RESUMO
Animals learn to prefer flavors associated with the intake of sugar (sucrose, fructose, glucose) and fat (corn oil: CO) solutions. Conditioned flavor preferences (CFP) have been elicited for sugars based on orosensory (flavor-flavor: e.g., fructose-CFP) and post-ingestive (flavor-nutrient: e.g., intragastric (IG) glucose-CFP) processes. Dopamine (DA) D1, DA D2 and NMDA receptor antagonism differentially eliminate the acquisition and expression of fructose-CFP and IG glucose-CFP. However, pharmacological analysis of fat (CO)-CFP, mediated by both flavor-flavor and flavor-nutrient processes, indicated that acquisition and expression of fat-CFP were minimally affected by systemic DA D1 and D2 antagonists, and were reduced by NMDA antagonism. Therefore, the present study examined whether systemic DA D1 (SCH23390), DA D2 (raclopride) or NMDA (MK-801) receptor antagonists altered acquisition and/or expression of CFP induced by oral glucose that should be mediated by both flavor-flavor and flavor-nutrient processes. Oral glucose-CFP was elicited following by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in 8% glucose and another flavor (CS-, e.g., grape) mixed in 2% glucose. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 2% glucose occurred 0.5 h after systemic administration of vehicle (VEH), SCH23390 (50-800 nmol/kg), raclopride (50-800 nmol/kg) or MK-801 (50-200 µg/kg). Rats displayed a robust CS+ preference following VEH treatment (94-95%) which was significantly though marginally attenuated by SCH23390 (67-70%), raclopride (77%) or MK-801 (70%) at doses that also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH, SCH23390 (50-400 nmol/kg), raclopride (50-400 nmol/kg) or MK-801 (100 µg/kg) 0.5 h prior to ten 1-bottle training trials with CS+/8%G and CS-/2%G training solutions that was followed by six 2-bottle CS+ vs. CS- tests in 2% glucose conducted without injections. The significant and persistent CS+ preferences observed in the VEH (94-98%) group was significantly reduced by rats receiving SCH23390 at 400 nmol/kg (65-73%), raclopride at 200 or 400 nmol/kg (76-82%) or MK-801 at 100 µg/kg (68-69%). Thus, systemic DA D1 and DA D2 receptor antagonism produced smaller reductions in the expression of oral glucose-CFP relative to fructose-CFP or IG-glucose-CFP. Correspondingly, systemic DA D1, DA D2 and NMDA receptor antagonism also produced smaller reductions in the acquisition of oral glucose-CFP relative to fructose-CFP or IG-glucose-CFP. These data suggest, but do not prove, that the magnitude and persistence of these receptor antagonist effects upon sugar-CFP might depend upon the individual or combined engagement of flavor-flavor and flavor-nutrient processes.
Assuntos
Condicionamento Psicológico/efeitos dos fármacos , Antagonistas dos Receptores de Dopamina D2/farmacologia , Preferências Alimentares/efeitos dos fármacos , Glucose/farmacologia , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Animais , Benzazepinas/farmacologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Preferências Alimentares/fisiologia , Masculino , Racloprida/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
Sugars and fats elicit innate and learned flavor preferences with the latter mediated by flavor-flavor (orosensory) and flavor-nutrient (post-ingestive) processes. Systemic dopamine (DA) D1 (SCH23390: SCH) and D2 (raclopride: RAC), but not opioid antagonists blocked the acquisition and expression of flavor-flavor preferences conditioned by sugars. In addition, systemic D1, but not D2 or opioid antagonists blocked the acquisition of flavor-nutrient preferences conditioned by intragastric (IG) sugar infusions. Given that DA antagonists reduce fat intake, the present study examined whether systemic D1 or D2 antagonists altered the acquisition and/or expression of conditioned flavor preferences (CFP) produced by pairing one novel flavor (CS+, e.g., cherry) with a 3.5% corn oil (CO: fat) solution relative to another flavor (CS-, e.g., grape) paired with a 0.9% CO solution. In an expression study, food-restricted rats were trained to drink either flavored 3.5% or 0.9% CO solutions on alternate days. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), SCH (50-800 nmol/kg) or RAC (50-800 nmol/kg). The rats displayed a robust CS+ preference following VEH treatment (87-88%) the expression of which was attenuated by treatment with moderate doses of RAC, and to a lesser degree, SCH. In an acquisition study, six groups of rats received VEH, SCH (25, 50, 200 nmol/kg) or RAC (50, 200 nmol/kg) 0.5 h prior to 1-bottle training trials with CS+ flavored 3.5% and CS- flavored 0.9% (CS-) CO solutions. A seventh Limited VEH group was trained with its training intakes limited to that of the SCH and RAC groups. Subsequent two-bottle tests were conducted with the CS+ and CS- flavors presented in 0.9% CO without injections. Significant and persistent CS+ preferences were observed in VEH (75-82%), Limited VEH (70-88%), SCH25 (75-84%), SCH50 (64-87%), SCH200 (78-91%) and RAC200 (74-91%) groups. In contrast, the group trained with RAC50 displayed a significant initial CS+ preference (76%) which declined over testing to 61%. These data indicate limited DA D1 and D2 receptor signaling involvement in the expression and acquisition of a fat-CFP relative to previous robust effects for sugar-CFP.
Assuntos
Gorduras na Dieta , Preferências Alimentares/fisiologia , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Paladar/fisiologia , Animais , Benzazepinas/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Preferências Alimentares/efeitos dos fármacos , Masculino , Racloprida/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de Dopamina D1/antagonistas & inibidores , Sacarina/farmacologia , Edulcorantes/farmacologia , Paladar/efeitos dos fármacosRESUMO
Animals learn to prefer flavors associated with the intake of dietary fats such as corn oil (CO) solutions. We previously reported that fat-conditioned flavor preferences in rats were relatively unaffected by systemic treatment with dopamine D1 and D2 antagonsits. The present study examined whether systemic opioid (naltrexone, NTX) or NMDA (MK-801) receptor antagonists altered the acquisition and/or expression of CO-CFP. The CFP was produced by training rats to drink one novel flavor (CS+, e.g., cherry) mixed in a 3.5% CO solution and another flavor (CS-, e.g., grape) in a 0.9% CO solution. In expression studies, food-restricted rats drank these solutions in one-bottle sessions (2 h) over 10 d. Subsequent two-bottle tests with the CS+ and CS- flavors mixed in 0.9% CO solutions occurred 0.5h after systemic administration of vehicle (VEH), NTX (0.1-5 mg/kg) or MK-801 (50-200 µg/kg). Rats displayed a robust CS+ preference following VEH treatment (85-88%) which was significantly though moderately attenuated by NTX (69-70%). The lower doses of MK-801 slightly reduced the CS+ preference; the high dose blocked the CS+ preference (49%) but also markedly reduced overall CS intake. In separate acquisition studies, rats received VEH or NTX (0.1, 0.5, 1mg/kg) or MK-801 (100 µg/kg) 0.5h prior to 1-bottle training trials with CS+/3.5% CO and CS-/0.9% CO training solutions. Additional Limited VEH groups were trained with intakes limited to that of the NTX and MK-801 groups. Subsequent two-bottle CS+ vs. CS- tests were conducted without injections. Significant and persistent CS+ preferences were observed in VEH (77-84%) and Limited VEH (88%) groups. NTX treatment during training failed to block the acquisition of CO-CFP although the magnitude of the CS+ preference was reduced by 0.5 (70%) and 1.0 (72%) mg/kg doses relative to the Limited VEH treatment (88%). In contrast, MK-801 (100 µg/kg) treatment during training blocked the acquisition of the CO-CFP. These data suggest a critical role for NMDA, but not opioid receptor signaling in the acquisition of a fat conditioned flavor preferences, and at best limited involvement of NMDA and opioid receptors in the expression of a previously learned preference.
Assuntos
Condicionamento Clássico/efeitos dos fármacos , Gorduras na Dieta , Ingestão de Alimentos/efeitos dos fármacos , Preferências Alimentares/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/fisiologia , Receptores Opioides/fisiologia , Animais , Regulação do Apetite/efeitos dos fármacos , Regulação do Apetite/fisiologia , Aprendizagem por Associação/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Comportamento Animal/fisiologia , Maleato de Dizocilpina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Masculino , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidoresRESUMO
The Mars Exploration Rover Opportunity identified the ferric sulphate mineral jarosite and possible relicts of gypsum at the Meridiani Planum landing site. On Earth, jarosite has been found to form in acid mine drainage environments, during the oxidation of sulphide minerals, and during alteration of volcanic rocks by acidic, sulphur-rich fluids near volcanic vents. Jarosite formation is thus thought to require a wet, oxidizing and acidic environment. But jarosite on Earth only persists over geologically relevant time periods in arid environments because it rapidly decomposes to produce ferric oxyhydroxides in more humid climates. Here we present equilibrium thermodynamic reaction-path simulations that constrain the range of possible conditions under which such aqueous alteration phases are likely to have formed on Mars. These calculations simulate the chemical weathering of basalt at relevant martian conditions. We conclude that the presence of jarosite combined with residual basalt at Meridiani Planum indicates that the alteration process did not proceed to completion, and that following jarosite formation, arid conditions must have prevailed.
Assuntos
Meio Ambiente Extraterreno/química , Compostos Férricos/análise , Compostos Férricos/química , Marte , Sulfatos/análise , Sulfatos/química , Água/química , Ácidos/química , Atmosfera/química , Sulfato de Cálcio/química , Sedimentos Geológicos/química , Concentração de Íons de Hidrogênio , Caulim/química , Minerais/química , Silicatos/química , TermodinâmicaRESUMO
Male rodents displayed greater magnitudes of analgesia following systemic, ventricular, and intracerebral administration of mu-opioid receptor agonists than female rodents. Whereas neonatal castration of male rat pups produced reductions in systemic and central morphine analgesia as adults, neonatal androgenization of female rat pups treated with testosterone propionate (TP) displayed enhancements in systemic and central morphine analgesia as adults. Adult gonadectomy minimally affected mu-opioid analgesia, except if less potent mu agonists were employed, or if morphine was directly administered into the ventrolateral periaqueductal gray (vlPAG). Adult ovariectomy failed to appreciably alter the enhanced analgesia following systemic morphine in female rats with neonatal androgenization. Because the vlPAG elicited morphine analgesia that was sensitive to both neonatal and adult gonadal hormone manipulations, the present study examined morphine analgesia elicited from the vlPAG in female rats receiving neonatal treatment with TP or vehicle and subsequently exposed to adult ovariectomy or sham surgery as well as intact male rats. Intact male rats displayed significantly greater magnitudes and potencies in vlPAG morphine analgesia than female rats receiving neonatal treatment with either vehicle or TP. In turn, neonatal androgenization significantly enhanced vlPAG morphine analgesia relative to neonatal vehicle treatment in females. Adult ovariectomy significantly enhanced the magnitude of vlPAG morphine analgesia in female rats receiving neonatal treatment with either vehicle or TP. This demonstrates a strong interaction between neonatal and adult gonadal hormone manipulations in the mediation of vlPAG morphine analgesia in female rats.
Assuntos
Androgênios/farmacologia , Morfina/farmacologia , Entorpecentes/farmacologia , Substância Cinzenta Periaquedutal/fisiologia , Propionato de Testosterona/farmacologia , Fatores Etários , Animais , Animais Recém-Nascidos , Castração/métodos , Estimulação Elétrica/métodos , Feminino , Masculino , Medição da Dor/métodos , Gravidez , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Fatores SexuaisRESUMO
Crystals of halite and sylvite within the Monahans (1998) H5 chondrite contain aqueous fluid inclusions. The fluids are dominantly sodium chloride-potassium chloride brines, but they also contain divalent cations such as iron, magnesium, or calcium. Two possible origins for the brines are indigenous fluids flowing within the asteroid and exogenous fluids delivered into the asteroid surface from a salt-containing icy object.
Assuntos
Meteoroides , Planetas Menores , Cloreto de Sódio , Água , Cristalização , Espectrometria de Massas , Cloreto de Potássio , Análise Espectral Raman , Temperatura , TexasRESUMO
How m-calpain is activated in cells has challenged investigators because in vitro activation requires near-millimolar calcium. Previously, we demonstrated that m-calpain activation by growth factors requires extracellular signal-regulated kinase (ERK); this enables tail deadhesion and allows productive motility. We now show that ERK directly phosphorylates and activates m-calpain both in vitro and in vivo. We identified serine 50 as required for epidermal growth factor (EGF)-induced calpain activation in vitro and in vivo. Replacing the serine with alanine limits activation by EGF and subsequent cell deadhesion and motility. A construct with the serine converted to glutamic acid displays constitutive activity in vivo; expression of an estrogen receptor fusion construct produces a tamoxifen-sensitive enzyme. Interestingly, EGF-induced m-calpain activation occurs in the absence of increased intracellular calcium levels; EGF triggers calpain even in the presence of intracellular calcium chelators and in calcium-free media. These data provide evidence that m-calpain can be activated through the ERK cascade via direct phosphorylation and that this activation may occur in the absence of cytosolic calcium fluxes.
Assuntos
Calpaína/metabolismo , Fator de Crescimento Epidérmico/farmacologia , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Substituição de Aminoácidos , Animais , Sequência de Bases , Sítios de Ligação , Cálcio/metabolismo , Calpaína/química , Calpaína/genética , Linhagem Celular , Movimento Celular , DNA Complementar/genética , Ativação Enzimática/efeitos dos fármacos , Humanos , Técnicas In Vitro , Sistema de Sinalização das MAP Quinases , Camundongos , Mutagênese Sítio-Dirigida , Fosforilação , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Serina/químicaRESUMO
GABA(A) and GABA(B) receptor agonists stimulate feeding following microinjection into the nucleus accumbens shell and ventral tegmental area, effects blocked selectively and respectively by GABA(A) and GABA(B) receptor antagonists. GABA antagonists also differentially alter opioid-induced feeding responses elicited from these sites. Although GABA agonists and antagonists have been shown to modulate feeding elicited by deprivation or glucoprivation, there has been no systematic examination of feeding elicited by homeostatic challenges following GABA antagonists in these sites. Therefore, the present study examined the dose-dependent ability of GABA(A) (bicuculline, 75-150 ng) and GABA(B) (saclofen, 1.5-3 microg) antagonists administered into the nucleus accumbens shell or ventral tegmental area upon feeding responses elicited by food deprivation (24 h), 2-deoxy-D-glucose-induced glucoprivation (500 mg/kg) or mercaptoacetate-induced lipoprivation (70 mg/kg). A site-specific effect of GABA receptor antagonism was observed for deprivation-induced feeding in that both bicuculline and saclofen administered into the nucleus accumbens shell, but not the ventral tegmental area, produced short-term (1-4 h), but not long-term (24-48 h) effects upon deprivation-induced intake without meaningfully altering body weight recovery. In contrast to the relative inability of GABA receptor antagonism in both sites to alter 2-deoxy-D-glucose-induced intake, mercaptoacetate-induced intake was eliminated by saclofen and significantly reduced by bicuculline in the nucleus accumbens shell and eliminated by both bicuculline and saclofen in the ventral tegmental area. These data reinforce the findings that GABA(A) and GABA(B) receptors in the nucleus accumbens shell and ventral tegmental area are not only important in the modulation of pharmacologically induced feeding responses, but also participate in differentially mediating the short-term feeding response to food deprivation in the nucleus accumbens shell as well strongly modulating lipoprivic, but not glucoprivic feeding responses in both sites.
Assuntos
Baclofeno/análogos & derivados , Bicuculina/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Privação de Alimentos/fisiologia , Antagonistas GABAérgicos/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Área Tegmentar Ventral/efeitos dos fármacos , Animais , Baclofeno/farmacologia , Comportamento Animal , Peso Corporal/efeitos dos fármacos , Desoxiglucose/farmacologia , Relação Dose-Resposta a Droga , Interações Medicamentosas , Ingestão de Alimentos/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Glucose/deficiência , Lipídeos/deficiência , Masculino , Ratos , Ratos Sprague-Dawley , Tioglicolatos/farmacologia , Fatores de TempoRESUMO
Human recombinant tumor necrosis factor (TNF) produces significant anorexia in the rat which persists for up to 24 h after a single dose (5 micrograms/325 g rat). Dose-response studies indicate similar potencies for TNF following central or peripheral administration. Brain 125I-TNF levels were more than 100-fold greater after intracerebroventricular than i.v. injection, whereas blood levels of radioactivity were quite similar following both routes of administration. Gel filtration chromatography and precipitation by trichloroacetic acid showed that the radioactive label which exited the central nervous system was associated with intact TNF. The rapid effusion of 125I-TNF from the central nervous system resulted in detection of similar levels of the cytokine in a number of important target tissues (skin, muscle, fat) relative to that detected after peripheral administration. After i.v. or intracerebroventricular administration, blood levels of TNF declined rapidly to nearly undetectable levels over 4 h. However, the anorexia induced by TNF was sustained, and feeding remained depressed between 6 and 24 h postadministration. These observations suggest that TNF produces its anorectic effects at peripheral sites, possibly through mediators.
Assuntos
Anorexia/induzido quimicamente , Ventrículos Cerebrais/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Transtornos da Alimentação e da Ingestão de Alimentos/induzido quimicamente , Fator de Necrose Tumoral alfa/toxicidade , Animais , Anorexia/fisiopatologia , Ventrículos Cerebrais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/toxicidade , Valores de Referência , Distribuição Tecidual , Fator de Necrose Tumoral alfa/administração & dosagem , Fator de Necrose Tumoral alfa/farmacocinéticaRESUMO
The ability of neuropeptide Y to potently stimulate food intake is dependent in part upon the functioning of mu and kappa opioid receptors. The combined use of selective opioid antagonists directed against mu, delta or kappa receptors and antisense probes directed against specific exons of the MOR-1, DOR-1, KOR-1 and KOR-3/ORL-1 opioid receptor genes has been successful in characterizing the precise receptor subpopulations mediating feeding elicited by opioid peptides and agonists as well as homeostatic challenges. The present study examined the dose-dependent (5-80 nmol) cerebroventricular actions of general and selective mu, delta, and kappa1 opioid receptor antagonists together with antisense probes directed against each of the four exons of the MOR-1 opioid receptor gene and each of the three exons of the DOR-1, KOR-1, and KOR-3/ORL-1 opioid receptor genes upon feeding elicited by cerebroventricular NPY (0.47 nmol, 2 ug). NPY-induced feeding was dose-dependently decreased and sometimes eliminated following pretreatment with general, mu, delta, and kappa1 opioid receptor antagonists. Moreover, NPY-induced feeding was significantly and markedly reduced by antisense probes directed against exons 1, 2, and 3 of the MOR-1 gene, exons 1 and 2 of the DOR-1 gene, exons 1, 2, and 3 of the KOR-1 gene, and exon 3 of the KOR-3/ORL-1 gene. Thus, whereas the opioid peptides, beta-endorphin and dynorphin A(1-17) elicit feeding responses that are respectively more dependent upon mu and kappa opioid receptors and their genes, the opioid mediation of NPY-induced feeding appears to involve all three major opioid receptor subtypes in a manner similar to that observed for feeding responses following glucoprivation or lipoprivation.
Assuntos
Comportamento Alimentar/efeitos dos fármacos , Antagonistas de Entorpecentes , Antagonistas de Entorpecentes/farmacologia , Neuropeptídeo Y/antagonistas & inibidores , Animais , Regulação do Apetite/fisiologia , Comportamento Animal/efeitos dos fármacos , Masculino , Antagonistas de Entorpecentes/administração & dosagem , Neuropeptídeo Y/farmacologia , Oligodesoxirribonucleotídeos Antissenso/genética , Oligodesoxirribonucleotídeos Antissenso/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores Opioides/genéticaRESUMO
Previous research has indicated the importance of sex in mediating the larger magnitude of mu-opioid receptor agonist-induced analgesia in male relative to female rodents. Whereas manipulations involving the adult activational effects of gonadal hormones minimally alter these analgesic sex differences, manipulations involving neonatal organizational effects of gonadal hormones have previously been shown to profoundly affect morphine analgesia. Thus, adult male rats neonatally castrated on the first day after birth displayed reductions in morphine analgesia relative to sham-operated males, and adult female rats neonatally treated with testosterone propionate on the first day after birth displayed enhancements in morphine analgesia relative to vehicle-treated females. Because neonatal androgenization in female rats produces an anovulatory syndrome that could change their adult hormonal milieu, the present study examined whether adult ovariectomy altered the magnitude of systemic morphine analgesia (1-5 mg/kg) in neonatal androgenized female rats relative to neonatal vehicle-treated female rats as well as gonadal steroid hormone replacement with estradiol benzoate. Intact male rats displayed significantly greater magnitudes and potencies (2- to 2.3-fold leftward shift) of systemic morphine analgesia than female rats treated neonatally with either vehicle (1-5 mg/kg) or testosterone (1.7-5 mg/kg). In turn, neonatal androgenized female rats displayed significantly greater magnitudes of systemic morphine (1, 5 mg/kg) analgesia than vehicle-treated female rats accompanied by a smaller 20% leftward shift in potency. Adult ovariectomy minimally affected morphine analgesia in neonatal vehicle-treated females, while significantly reducing the magnitude (1 mg/kg), but not the potency of morphine analgesia in neonatal androgenized female rats. Estradiol replacement therapy significantly increased the magnitude of morphine analgesia in both groups at some doses, but only changed the potency (20-30%) in females treated neonatally with vehicle. Taken together, these data suggest a limited organizational-activational gonadal hormone interaction in the mediation of systemic morphine analgesia in female rats.
Assuntos
Analgésicos Opioides/farmacologia , Estradiol/metabolismo , Gônadas/metabolismo , Morfina/farmacologia , Caracteres Sexuais , Testosterona/metabolismo , Analgésicos Opioides/metabolismo , Animais , Relação Dose-Resposta a Droga , Tolerância a Medicamentos/fisiologia , Estradiol/farmacologia , Feminino , Masculino , Morfina/metabolismo , Ovariectomia , Ovário/metabolismo , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testosterona/farmacologiaRESUMO
Overconsumption of nutrients high in fats and sugars can lead to obesity. Previous studies indicate that sugar or fat consumption activate individual brain sites using Fos-like immunoreactivity (FLI). Sugars and fats also elicit conditioned flavor preferences (CFP) that are differentially mediated by flavor-flavor (orosensory: f/f) and flavor-nutrient (post-ingestive: f/n) processes. Dopamine (DA) signaling in the medial prefrontal cortex (mPFC), the amygdala (AMY) and the nucleus accumbens (NAc), has been implicated in acquisition and expression of fat- and sugar-CFP. The present study examined the effects of acute consumption of fat (corn oil: f/f and f/n), glucose (f/f and f/n), fructose, (f/f only), saccharin, xanthan gum or water upon simultaneous FLI activation of DA mesotelencephalic nuclei (ventral tegmental area (VTA)) and projections (infralimbic and prelimbic mPFC, basolateral and central-cortico-medial AMY, core and shell of NAc as well as the dorsal striatum). Consumption of corn oil solutions, isocaloric to glucose and fructose, significantly increased FLI in all sites except for the NAc shell. Glucose intake significantly increased FLI in both AMY areas, dorsal striatum and NAc core, but not in either mPFC area, VTA or Nac shell. Correspondingly, fructose intake significantly increased FLI in the both AMY areas, the infralimbic mPFC and dorsal striatum, but not the prelimbic mPFC, VTA or either NAc area. Saccharin and xanthan gum intake failed to activate FLI relative to water. When significant FLI activation occurred, highly positive relationships were observed among sites, supporting the idea of activation of a distributed brain network mediating sugar and fat intake.
Assuntos
Encéfalo/metabolismo , Neurônios Dopaminérgicos/metabolismo , Ingestão de Alimentos , Neurônios/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Tonsila do Cerebelo/metabolismo , Animais , Óleo de Milho/administração & dosagem , Frutose/administração & dosagem , Glucose/administração & dosagem , Masculino , Neostriado/metabolismo , Núcleo Accumbens/metabolismo , Polissacarídeos Bacterianos/administração & dosagem , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Sprague-Dawley , Sacarina/administração & dosagem , Tirosina 3-Mono-Oxigenase/metabolismo , Área Tegmentar Ventral/metabolismo , Água/administração & dosagemRESUMO
Extensive evidence has indicated that distinct neural systems specifically designed to inhibit sensitivity to painful stimuli exist. Recent advances suggest that the endorphins, enkephalins and the opiate receptor interact with a descending serotonergic bulbospinal system to mediate the analgesic responses to opiates and electrical stimulation. In assessing the evolutionary and behavioral significance of this pain-inhibitory system, several laboratories discovered that acute exposure to a wide variety of stressful events results in a transient analgesia. Chronic exposure to a number of these stressors results in adaptation of the analgesic response. The purpose of this review is to identify and characterize the mechanisms by which these stressors activate pain-inhibition. The relationship of stress-induced analgesia to each of the following is reviewed: (a) the role of endorphins, enkephalins and the opiate receptor; (b) the role of the descending serotonergic bulbospinal system; (c) the role of the pituitary gland; and (d) the role of hypothalamic mechanisms. Data will be discussed in terms of "opiate" and "non-opiate" pain-inhibitory mechanisms, in which some stressors act through the former and other stressors act through the latter.
Assuntos
Sistema Nervoso Central/fisiopatologia , Hormônios/fisiologia , Dor/fisiopatologia , Estresse Fisiológico/fisiopatologia , Analgesia , Animais , Desoxiglucose/farmacologia , Sinergismo Farmacológico , Tolerância a Medicamentos , Vias Eferentes/fisiopatologia , Hipotálamo/fisiopatologia , Mesencéfalo/fisiopatologia , Morfina/farmacologia , Naloxona , Hipófise/fisiopatologia , Núcleos da Rafe/fisiopatologia , Ratos , Limiar Sensorial , Serotonina/fisiologia , Medula Espinal/fisiopatologia , Substância Gelatinosa/fisiopatologiaRESUMO
The demonstrated existence of opioid and nonopioid forms of pain control has raised questions as to how they interact. Previous indirect evidence suggests that activation of one system inhibited the activation of the other. The present study assessed this directly using morphine as an opiate form of analgesia and continuous cold-water swims (CCWS, 4 degrees C, 2 min) as the nonopioid form. A significant reduction in morphine (8 mg/kg, SC) analgesia on the tail-flick test was observed if rats were acutely exposed to CCWS immediately prior to morphine administration. The inability of naloxone (10 mg/kg, SC) to reduce CCWS analgesia verified its nonopioid nature. The antagonism of morphine (3 mg/kg, SC) analgesia was greater following preexposure to 2 min of CCWS than 1 min of CCWS. CCWS was also more effective in antagonizing analgesia induced by the 3 mg/kg than the 8 mg/kg dose of morphine. The antagonism of morphine analgesia by CCWS was dependent upon the temporal patterning of stimulus presentation: exposure to CCWS 20 or 60 min prior to morphine failed to alter subsequent morphine analgesia. A significant reduction in analgesia induced by intraperitoneal administration of morphine (10 mg/kg) was also observed when CCWS was presented immediately prior to injection, suggesting that pharmacokinetic factors such as altered drug absorbance by CCWS-induced vasoconstriction do not appear to explain these effects. These data provide direct support for the existence of collateral inhibitory mechanisms activated by CCWS and morphine, and suggests that these opioid and nonopioid forms of analgesia do not function synergistically, but instead involve some form of hierarchical order.
Assuntos
Analgesia , Temperatura Baixa , Morfina/farmacologia , Inibição Neural , Animais , Injeções Intraperitoneais , Masculino , Ratos , Ratos EndogâmicosRESUMO
Although age-related reductions in levels of opiate receptors and endogenous opioid peptides have been observed in rats, effects of aging upon basal pain thresholds and morphine analgesia have not indicated clear results. The present study evaluated the dose-dependent (1,2.5, 5 and 10 mg/kg, SC) and time-dependent (30, 60, 90, 180 min) properties of morphine analgesia on two nociceptive measures (tail-flick latencies and jump thresholds) across five age cohorts of rats (4, 9, 14, 19 and 24-months of age). To ascertain whether any changes were the result of specific alterations in pain inhibition or an overall shift in opiate responses, effects upon morphine-induced hyperthermia were also evaluated. Age-related effects upon morphine analgesia on the tail-flick test exhibited a biphasic pattern with the three older age groups displaying significant decreases in morphine analgesia 30 min after injection and significant increases in morphine analgesia 180 min after injection. Age-related effects upon morphine analgesia on the jump test revealed equivilent reductions in analgesic magnitude across doses for the three older cohorts. In contrast, morphine hyperthermia displayed small inconsistent changes across cohorts. The reductions in morphine analgesia in older animals could not be attributed to changes in either baseline pain thresholds or delayed peripheral absorption and/or clearance of the drug. Rather, the reductions in morphine analgesia in older animals complement the recent findings of similar age-related reductions in the analgesic responses induced by exposure to several environmental stressors.
Assuntos
Envelhecimento , Temperatura Corporal/efeitos dos fármacos , Morfina/farmacologia , Dor/tratamento farmacológico , Animais , Feminino , Dor/diagnóstico , Ratos , Ratos Endogâmicos , Limiar SensorialRESUMO
Age-related decreases occur in analgesic responses following morphine, 2-deoxy-D-glucose, inescapable foot shock and cold-water swims. Decreased affinity and concentration of opiate receptors and levels of endogenous opioids are also observed. The present study evaluated the dose-dependent (0.1, 0.5, 1.0, 5.0 micrograms, ICV) and time-dependent (15, 30, 45, 60 min) properties of beta-endorphin analgesia on the jump test across three age cohorts of rats (8, 18 and 30 months of age). The different age cohorts failed to display differences in the magnitude of beta-endorphin analgesia across doses and times, except for a transient (30 min) decrease in the 30-month group following the 0.5 microgram dose. This maintenance of beta-endorphin analgesia across age cohorts stands in marked contrast to the age-related decrements in morphine and opiate-sensitive environmental analgesia and occurs despite decreased levels of beta-endorphin. These data are discussed in terms of differential alterations in opiate receptor subpopulations, and represent the first instance of maintained opioid analgesia across cohorts.
Assuntos
Analgesia , Ventrículos Cerebrais/crescimento & desenvolvimento , Endorfinas/farmacologia , Morfina/farmacologia , Envelhecimento , Animais , Ventrículos Cerebrais/efeitos dos fármacos , Relação Dose-Resposta a Droga , Endorfinas/administração & dosagem , Feminino , Injeções Intraventriculares , Ratos , Ratos Endogâmicos , beta-EndorfinaRESUMO
The endogenous ligand for the orphan opioid receptor, orphanin FQ/nociceptin (OFQ), has recently been characterized. The OFQ peptide sequence contains paired basic amino acids, suggesting the possibility of posttranslational processing to a peptide containing the first 11 amino acids of the OFQ peptide. This peptide has been reported in the brain and it has a unique pharmacology. In the present study, we compared the autoradiographic distribution of (125)I[Tyr(14)]OFQ and (125)I[Tyr(10)]OFQ(1-11) in coronal rat brain sections. Nonspecific binding was defined with unlabeled OFQ or OFQ(1-11), respectively. Both radioligands demonstrated high levels of specific binding (>95% of total binding), with no appreciable binding in white matter areas with either ligand. (125)I[Tyr(14)]OFQ binding was widely distributed throughout the rat brain. In contrast, (125)I[Tyr(10)]OFQ(1-11) binding was more restricted. The highest (125)I[Tyr(14)]OFQ binding levels measured in this study were found in the locus coeruleus, an area which contained very low (125)I[Tyr(10)]OFQ(1-11) binding. Both ligands labeled the cortex, hippocampus and amygdala. In the thalamus, (125)I[Tyr(14)]OFQ binding was prominent in most nuclei, whereas (125)I[Tyr(10)]OFQ(1-11) binding was restricted to the midline thalamus. (125)I[Tyr(14)]OFQ binding was heavy in the suprachiasmatic hypothalamus, and moderate in other hypothalamic nuclei. (125)I[Tyr(10)]OFQ(1-11) binding in the hypothalamus, however, was present mainly in the ventromedial hypothalamic nucleus. Lower binding levels of both ligands were found in the caudate putamen. The distinct autoradiographic patterns of these two ligands are consistent with different binding sites, which might help explain their different functional activities.
Assuntos
Sítios de Ligação/fisiologia , Química Encefálica/fisiologia , Encéfalo/citologia , Encéfalo/metabolismo , Peptídeos Opioides/metabolismo , Fragmentos de Peptídeos/metabolismo , Animais , Mapeamento Encefálico , Diencéfalo/citologia , Diencéfalo/metabolismo , Radioisótopos do Iodo , Mesencéfalo/citologia , Mesencéfalo/metabolismo , Metencéfalo/citologia , Metencéfalo/metabolismo , Ensaio Radioligante , Ratos , Ratos Sprague-Dawley , Telencéfalo/citologia , Telencéfalo/metabolismo , Tirosina/metabolismo , NociceptinaRESUMO
The cholecystokinin antagonist proglumide potentiates morphine analgesia. To understand more fully the opiate receptor subtypes involved with this effect, we investigated the effect of proglumide on spinal and supraspinal mu and spinal delta analgesia in mice. Proglumide alone had no effect on tailflick latencies, but increased, in a dose-dependent manner, tailflick latencies in morphine-tolerant mice. Proglumide also potentiated morphine analgesia in naive mice in a dose-dependent manner, with a maximal effect at 5-10 mg/kg. Proglumide both shifted the dose-response curve for morphine analgesia to the left and prolonged morphine's duration of action. Proglumide increased the sensitivity of supraspinal mu 1 receptor mechanisms of analgesia without influencing spinal mechanisms. Proglumide administered subcutaneously potentiated the analgesic actions of intracerebroventricular [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAGO; (mu 1), but not intrathecal DAGO (mu 2) or [D-Pen2,D-Pen5]enkephalin (DPDPE; delta). The selective mu 1 receptor antagonist naloxonazine blocked proglumide-enhanced morphine analgesia.
Assuntos
Glutamina/análogos & derivados , Entorpecentes/farmacologia , Proglumida/farmacologia , Receptores Opioides/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Ala(2)-MePhe(4)-Gly(5)-Encefalina , D-Penicilina (2,5)-Encefalina , Encefalinas/farmacologia , Masculino , Camundongos , Morfina/farmacologia , Dependência de Morfina/fisiopatologia , Tempo de Reação/efeitos dos fármacos , Receptores Opioides/metabolismo , Receptores Opioides delta , Receptores Opioides muRESUMO
A comparison of the effects of the short-acting opioid antagonist naloxone, with the irreversible and highly-specific mu-1 antagonist naloxonazine, has categorized the mediation of opioids in some forms of feeding into mu-1 and non-mu-1 components. The mu-1 sites have been implicated in free-feeding, deprivation-induced feeding and morphine-induced hyperphagia, based upon their sensitivity to both naloxone and naloxonazine. However, the ability of naloxone, but not naloxonazine to inhibit feeding, induced by either 2-deoxy-D-glucose glucoprivation, ethylketocyclazocine, dynorphin or (D-ala2., D-leu5.)-enkephalin implies the existence of non-mu-1 opioid receptor mechanisms in these responses. The present study compared the effects of the daily administration of naloxone and naloxonazine (10 mg/kg, i.v.) in rats in three different types of maturational or dietary situations. In adult rats, naloxonazine and naloxone significantly reduced body weight (7% and 4%, respectively) and food intake (21% and 13%, respectively) over 14 days. These effects were more pronounced in adolescent rats where naloxonazine and naloxone significantly reduced the gain in body-weight (53% and 33%, respectively) and food intake (24% and 15%, respectively) over 14 days. In the adolescent rats, the effects of naloxonazine were significantly greater than those of naloxone. In contrast, chronic treatment with neither naloxone nor naloxonazine altered body weight or food intake of rats made obese by dietary manipulations and left on that diet during treatment with antagonist.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Peso Corporal/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Naloxona/análogos & derivados , Naloxona/farmacologia , Envelhecimento/metabolismo , Animais , Depressores do Apetite/farmacologia , Masculino , Naloxona/administração & dosagem , Ratos , Ratos EndogâmicosRESUMO
Neonatal administration of monosodium glutamate (MSG) destroyed perikarya in the arcuate nucleus and median eminence, including those that contain met-enkephalin and beta-endorphin and it increased the density of opiate receptors in the midbrain. Treatment with glutamate decreased the analgesic response on the jump test following a 10 mg/kg dose of morphine, yet increased the analgesic response on the hot-plate test following 1 mg/kg dose of morphine. The present study demonstrated that changes in morphine-induced analgesia induced by glutamate varied as functions of the pain test and of gender. While males treated with glutamate displayed attenuated analgesia induced by morphine (2.5-15 mg/kg) on the jump test, jump thresholds of females treated with glutamate were potentiated after a 10 mg/kg dose of morphine and attenuated after a 15 mg/kg dose of morphine, relative to controls. In contrast, analgesia on the hot-plate test was potentiated in animals of both genders treated with glutamate after all doses of morphine. Changes in tolerance to morphine induced by glutamate also depended on the pain test and gender. While the peak analgesic response on the jump test did not occur until the fifth injection of morphine in all rats treated with glutamate, tolerance on the jump test was subsequently retarded in males treated with glutamate and accelerated in glutamate-treated females. Tolerance on the hot-palate test appeared not to be consistently affected by treatment with glutamate. Morphine-induced hyperthermia was initially decreased in rats treated with glutamate, but subsequently decreased in glutamate-treated males and increased in glutamate-treated females.(ABSTRACT TRUNCATED AT 250 WORDS)