RESUMO
In order to localize the site of action of neuropeptides in relation to their effects on behavior and memory various approaches have been used. As a result of studies using rats bearing lesions in different areas of the limbic system as well as of studies in which neuropeptides were locally applied into various areas of the brain it appeared that the limbic system (amygdala, hippocampus, septum and some thalamic areas) plays an essential role in the effect of vasopressin and ACTH and their derivatives on behavior and memory. Neurochemical studies generally indicate that changes occur in catecholamine utilization in these various limbic regions upon administration of these neuropeptides. It can be concluded that the effects of vasopressin in the terminal regions of the coeruleo-telencephalic noradrenalin system correlate with its effects on consolidation of memory. It is likely that the effects of vasopressin on other transmitter systems (e.g. dopamine in the amygdala and serotonin in the hippocampus) correspond with the effect of this neuropeptide on retrieval processes. In addition, regional differences in biotransformation of the neurohypophyseal hormones suggest that different patterns of behaviorally active fragments of these peptides may be present locally in the brain.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Comportamento Animal/efeitos dos fármacos , Sistema Límbico/efeitos dos fármacos , Hormônios Neuro-Hipofisários/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Catecolaminas/metabolismo , Condicionamento Psicológico/efeitos dos fármacos , Extinção Psicológica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Lipressina/farmacologia , Hormônios Estimuladores de Melanócitos/farmacologia , Vias Neurais/efeitos dos fármacos , Ocitocina/farmacologia , Ratos , Septo Pelúcido/efeitos dos fármacos , Núcleos Talâmicos/efeitos dos fármacosRESUMO
To investigate the role of brain catecholamines in the development of spontaneous hypertension, rats were treated with different doses of the neurotoxins 6-hydroxydopamine (6-OHDA) or DSP-4 (N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine hydrochloride). Intracerebroventricular (i.c.v.) 6-OHDA attenuated the development of hypertension in spontaneously hypertensive rats (SHR) and also lowered the systolic blood pressure (BP) in Wistar-Kyoto (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP). Norepinephrine was markedly and dose-dependently depleted in brain areas of all three substrains. Dopamine was affected also, although to a lesser extent. Pretreatment with the norepinephrine-uptake inhibitor desmethylimipramine (DMI) did not influence the effect of 6-OHDA on the development of hypertension in SHR. DMI largely antagonized the 6-OHDA-induced depletion of brain norepinephrine, while dopamine depletion was not affected. Specific depletion of brain norepinephrine by treatment with DSP-4 did not alter the rise in BP in SHR. These results suggest that the effect of 6-OHDA on the development of hypertension in SHR may not be mediated through destruction of brain norepinephrine neurons, but that interruption of brain dopaminergic mechanisms is a possibility in this respect.
Assuntos
Encéfalo/metabolismo , Dopamina/fisiologia , Hipertensão/fisiopatologia , Animais , Benzilaminas/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Desipramina/farmacologia , Dopamina/análise , Dopamina/metabolismo , Relação Dose-Resposta a Droga , Hidroxidopaminas/farmacologia , Hipertensão/induzido quimicamente , Injeções Intraventriculares , Masculino , Norepinefrina/análise , Norepinefrina/metabolismo , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKYRESUMO
Cerebral infarction volume after occlusion of a short proximal segment of the middle cerebral artery (MCA) is reported to be different in Wistar compared to Fischer-344 (F344) rats, in both size and variability. Knowledge about the cause of these differences might enable us to explain and perhaps reduce the variation in infarct volume and create a reproducible model of focal cerebral ischemia in the rat. We investigated in Wistar and F344 rats both the effect of occlusion of a long proximal MCA segment on cerebral infarction volume, visualized by magnetic resonance imaging and histology, and the morphology of the major cerebral arteries. Occlusion of a long proximal MCA segment resulted in a striatal and a small cortical infarction in Wistar and a striatal and sizable cortical infarction in F344 rats (as is the case after occlusion of a short proximal MCA segment). In Wistar rats, however, occlusion of a long proximal MCA segment strongly reduced the variability in infarction volume in comparison to occlusion of a small proximal MCA segment. Analysis of the morphology of the major cerebral arteries showed a significantly higher number of proximal side branches of the long proximal MCA segment in Wistar rates than in F344 rats. We conclude that after short-segment proximal MCA occlusion, extreme variability in cerebral infarction volume in Wistar rats compared to F344 rats may be attributable to a significantly greater number of proximal MCA side branches in Wistar rats than in F344 rats.
Assuntos
Artérias Cerebrais , Modelos Animais de Doenças , Ataque Isquêmico Transitório/patologia , Ataque Isquêmico Transitório/fisiopatologia , Animais , Artérias Cerebrais/patologia , Artérias Cerebrais/fisiopatologia , Constrição , Imageamento por Ressonância Magnética , Masculino , Ratos , Ratos Endogâmicos F344 , Ratos Wistar , Especificidade da EspécieRESUMO
The effects of oxytocin, administered intracerebroventricularly in doses of 1, 10, 100 and 1000 pmol, were studied on the disappearance of catecholamines induced by alpha-methyl-p-tyrosine in microdissected nuclei of the rat brain. Oxytocin dose-dependently decreased the utilization of noradrenaline in the lateral and medial septal nuclei and anterior hypothalamic area, whereas an enhanced utilization was observed in the nucleus supraopticus. Tendency towards a change in utilization of noradrenaline was found in the dorsal septal nucleus and the lateral amygdala. Utilization of dopamine was not significantly affected in any of the nuclei of the brain studied. Tendency towards a decrease in utilization of dopamine was observed in the nucleus caudatus, globus pallidus and medial septal nucleus. It thus appears that oxytocin elicited changes in only a restricted number of brain nuclei. Interestingly, these nuclei contain cell bodies (nucleus supraopticus) and terminals (other nuclei) of the oxytocin system in the brain. Though the effects of oxytocin were not as widespread as those previously seen after administration of vasopressin, it is worthy of note that, in general, the effects of oxytocin were opposite to those seen after vasopressin. The opposite effects of vasopressin and oxytocin on catecholamine metabolism could be related to the opposite effects of the two peptides on behaviour, neuroendocrine and autonomic regulation.
Assuntos
Química Encefálica/efeitos dos fármacos , Sistema Límbico/metabolismo , Norepinefrina/metabolismo , Ocitocina/farmacologia , Animais , Injeções Intraventriculares , Masculino , Metiltirosinas/farmacologia , Ratos , Ratos Endogâmicos , alfa-MetiltirosinaRESUMO
1. We investigated the effects of [Nle4,D-Phe7]alpha-melanocyte-stimulating hormone (NDP-MSH), adrenocorticotropin-(1-24) (ACTH-(1-24)) and gamma 2-MSH, three melanocortins with different agonist selectivity for the five cloned melanocortin receptors, on blood pressure and heart rate in conscious, freely moving rats following intravenous administration. 2. As was previously found by other investigators as well as by us gamma 2-MSH, a peptide suggested to be an agonist with selectivity for the melanocortin MC3 receptor, caused a dose-dependent, short lasting pressor response in combination with a tachycardia. Despite the fact that NDP-MSH is a potent agonist of various melanocortin receptor subtypes, among which the melanocortin MC1 receptor, it did not affect blood pressure or heart rate, when administered i.v. in doses of up to 1000 nmol kg-1. 3. ACTH-(1-24) caused a dose-dependent decrease in blood pressure in combination with a dose-dependent increase in heart rate in a dose-range from 15 to 500 nmol kg-1. The cardiovascular effects of ACTH-(1-24) were independent of the presence of the adrenals. 4. Pretreatment with ACTH-(1-24) caused a pronounced, dose-dependent parallel shift to the right of the dose-response curve for the pressor and tachycardiac effects of gamma 2-MSH. The antagonistic effect of ACTH-(1-24) was already apparent following a dose of this peptide as low as 10 nmol kg-1, which when given alone had no intrinsic hypotensive activity. 5. These results form further support for the notion that it is not via activation of one of the as yet cloned melanocortin receptors that gamma-MSH-like peptides increase blood pressure and heart rate. The cardiovascular effects of ACTH-(1-24) seem not to be mediated by the adrenal melanocortin MC3 receptors, for which ACTH-(1-24) is a selective agonist, or by adrenal catecholamines. 6. There appears to be a functional antagonism between ACTH-(1-24) and gamma 2-MSH, two melanocortins derived from a common precursor, with respect to their effect on blood pressure and heart rate. Whether this antagonism plays a (patho)physiological role remains to be shown.
Assuntos
Hormônio Adrenocorticotrópico/química , Fragmentos de Peptídeos/farmacologia , alfa-MSH/análogos & derivados , Medula Suprarrenal/fisiologia , Medula Suprarrenal/cirurgia , Adrenalectomia , Animais , Pressão Sanguínea/efeitos dos fármacos , Antagonismo de Drogas , Frequência Cardíaca/efeitos dos fármacos , Masculino , Fenilefrina/farmacologia , Ratos , Ratos Wistar , alfa-MSH/farmacologiaRESUMO
The protein kinase C activator 4 beta-phorbol 12,13-dibutyrate (PDB) enhanced in a concentration-dependent manner the electrically stimulated release of [3H]noradrenaline ([3H]NA) and [3H]dopamine ([3H]DA) from rat amygdala slices in vitro. PDB enhanced the basal release of [3H]NA and [3H]DA as well. 4 alpha-Phorbol 12,13-didecanoate, which lacks the capacity to activate protein kinase C, was without effect on either basal or electrically stimulated release of [3H]NA and [3H]DA. Polymyxin B, which is a relatively selective protein kinase C inhibitor, decreased in a concentration-dependent manner the electrically stimulated release of both [3H]NA and [3H]DA from amygdala slices, whereas it enhanced the basal release of both neuromessengers. In the presence of 1.5 X 10(-7) M PDB, a concentration which when added to the superfusion medium alone doubled the electrically stimulated release of both [3H]NA and [3H]DA, polymyxin B again decreased in a concentration-dependent manner the release of both neuromessengers. At all polymyxin B concentrations used, the effect of the PKC inhibitor, expressed as percent inhibition, in the presence of PDB was approximately the same as that observed in the absence of PDB. This suggests that the antagonism between PDB and polymyxin B at the level of protein kinase C is not a competitive one. The effects of PDB and polymyxin B on basal release were additive. Taken together, these data suggest that in the amygdala presynaptically localized protein kinase C plays a role in signal transduction processes related to the exocytotic secretion of NA and DA from their nerve terminals.
Assuntos
Tonsila do Cerebelo/metabolismo , Dopamina/metabolismo , Norepinefrina/metabolismo , Ésteres de Forbol/farmacologia , Polimixina B/farmacologia , Polimixinas/farmacologia , Tonsila do Cerebelo/efeitos dos fármacos , Tonsila do Cerebelo/fisiologia , Animais , Estimulação Elétrica , Técnicas In Vitro , Masculino , Dibutirato de 12,13-Forbol , Ratos , Ratos EndogâmicosRESUMO
ACTH-(1-24) enhanced the basal as well as the electrically stimulated release of [3H]dopamine from rat septal slices in vitro. In the absence of Ca2+ from the superfusion medium the effect of ACTH-(1-24) on the electrically stimulated release of [3H]dopamine was abolished. The stimulus-evoked release of [3H]dopamine from septal slices appeared to be modulated through dopamine receptors of the D2 subtype: the dopamine D2 receptor agonists 2-(N-propyl-N-2-thienylethylamino)-5-hydroxytetralin (N-0437) and quinpirole reduced, whereas the dopamine D2 receptor antagonist sulpiride enhanced the electrically stimulated release of [3H]dopamine. The magnitude of the effect of ACTH-(1-24) on [3H]dopamine release was the same in the presence or absence of N-0437, quinpirole and sulpiride. ACTH-(1-24) had no effect on either the basal or the electrically stimulated release of [3H]noradrenaline. Also when the electrically stimulated release of [3H]noradrenaline was reduced by the alpha 2-adrenoceptor agonist clonidine, the peptide was without effect. These results show that ACTH-(1-24) selectively enhances the release of [3H]dopamine from septal slices. The effect of the peptide is independent of the degree of activation of dopamine D2 receptors which modulate the stimulus-evoked release of [3H]dopamine. These results suggest that ACTH-(1-24) enhances the stimulus-evoked release of dopamine in the septum via a mechanism not associated with dopamine D2 autoreceptors.
Assuntos
Cosintropina/farmacologia , Dopamina/metabolismo , Receptores Dopaminérgicos/metabolismo , Septo Pelúcido/metabolismo , Hormônio Adrenocorticotrópico , Animais , Antagonistas de Dopamina , Estimulação Elétrica , Ergolinas/farmacologia , Técnicas In Vitro , Masculino , Norepinefrina/metabolismo , Quimpirol , Ratos , Ratos Endogâmicos , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de Dopamina D2 , Núcleos Septais/efeitos dos fármacos , Núcleos Septais/metabolismo , Núcleos Septais/fisiologia , Septo Pelúcido/efeitos dos fármacos , Septo Pelúcido/fisiologia , Sulpirida/farmacologiaRESUMO
Administration of arginine-vasopressin (AVP, 5 micrograms, s.c.) immediately after the learning trial results in a long-term facilitation of a one-trial learning passive avoidance response. This effect of AVP is absent in animals with prior destruction of the ascending dorsal noradrenergic bundle by bilateral microinjection of 6-hydroxydopamine (6-OHDA). Postlearning local microinjection of a minute amount of AVP via chronically implanted cannulae into the locus coeruleus did not influence passive avoidance behavior. Upon injection into the midbrain dorsal raphe nucleus, however AVP facilitated passive avoidance behavior. This effect, however, was absent in rats receiving previous microinjection of 5,6-dihydroxytryptamine (5,6-DHT) or of 6-OHDA into the dorsal raphe nucleus. Bilateral 6-OHDA-induced lesions of the nucleus accumbens or 5,6-DHT-induced destruction of the dorsal raphe nucleus did not prevent the effect of AVP administered subcutaneously. The data suggest that vasopressin facilitates memory consolidation processes by modulating noradrenergic neurotransmission in terminals of the dorsal noradrenergic bundle. The serotoninergic neuronal network originating from the dorsal raphe nucleus has a secondary--norepinephrine-mediated--influence upon these processes.
Assuntos
Arginina Vasopressina/farmacologia , Locus Cerúleo/efeitos dos fármacos , Memória/efeitos dos fármacos , Norepinefrina/metabolismo , Retenção Psicológica/efeitos dos fármacos , 5,6-Di-Hidroxitriptamina/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Dopamina/metabolismo , Hidroxidopaminas/farmacologia , Masculino , Mesencéfalo/efeitos dos fármacos , Vias Neurais/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Núcleos da Rafe/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Tempo de Reação/efeitos dos fármacos , Serotonina/metabolismoRESUMO
The results of the present experiments show that local microinjections of Arg8-vasopressin into the nucl. caudatus cause an increase in the alpha-methyl-p-tyrosine methylester-HCl-induced disappearance of dopamine (DA) at the site of administration of the peptide. It is suggested that the caudate nucleus is the site of action of the peptide with respect to its effect on nigrostriatal DA neurons. This conclusion is corroborated by both the finding that microinjection of Arg8-vasopressin into the A9 region, which contains the cell bodies of the nigrostriatal system, was ineffective, and the results of push-pull experiments which showed an enhancement in apparent DA release in the nucl. caudatus when Arg8-vasopressin was co-perfused through the cannula system. Arg8-vasopressin appears to have a rather modest effect on nucl. caudatus DA synthesis, as was deduced from the results of experiments in which the in vitro conversion of tritiated tyrosine into tritiated DA was measured following in vivo Arg8-vasopressin administration as well as after in vitro incubation with the peptide. In conclusion, the interaction of vasopressin with the nigrostriatal DA system appears to be at the level of the DA terminals in the nucl. caudatus rather than at the level of the substantia nigra, and secondly, Arg8-vasopressin appears to affect DA release in the nucl. caudatus rather than DA synthesis.
Assuntos
Arginina Vasopressina/farmacologia , Núcleo Caudado/efeitos dos fármacos , Dopamina/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Núcleos Septais/efeitos dos fármacos , Substância Negra/efeitos dos fármacos , Animais , Núcleo Caudado/metabolismo , Técnicas In Vitro , Masculino , Vias Neurais/efeitos dos fármacos , Norepinefrina/biossíntese , Ratos , Tirosina/metabolismoRESUMO
Rats which had received bilateral microinjections of 1:50 diluted anti-vasopressin serum into the dorsal or ventral hippocampus, immediately after the learning trial of a one-trial passive avoidance test, showed a reduction in avoidance latency scores during subsequent retention tests 24 and 48 h later. Postlearning microinjection of anti-vasopressin serum into either the dorsolateral septum or the caudate nucleus was without effect on the retention of passive avoidance behavior. Microinjection of anti-vasopressin serum 1 h before the 24-h retention session into either the dorsal hippocampus, the ventral hippocampus or the dorsolateral septum attenuated avoidance responding during both the 24-h and 48-h retention sessions, whereas preretention microinjection of the serum into the caudate nucleus was not effective. Intracerebroventricular administration of the anti-vasopressin serum in amounts similar to those used in the microinjection experiments did not affect retention scores when given either immediately after the learning trial or before the first retention session. One week after the behavioral experiments, a repeated microinjection of anti-vasopressin serum decreased the local alpha-methyl-p-tyrosine methylester (alpha-MPT)-induced disappearance of noradrenaline in the ventral hippocampus and the dorsal hippocampus respectively. Microinjection of the antiserum in the dorsolateral septum enhanced noradrenaline disappearance in this brain region. No effect was found on alpha-MPT-induced dopamine disappearance in the caudate nucleus following local microinjection of anti-vasopressin serum.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/metabolismo , Catecolaminas/metabolismo , Soros Imunes/farmacologia , Sistema Límbico/fisiologia , Vasopressinas/imunologia , Animais , Aprendizagem da Esquiva/fisiologia , Soros Imunes/administração & dosagem , Masculino , Microinjeções , Ratos , Ratos EndogâmicosRESUMO
The accumulation of serotonin induced by the monoamino oxidase inhibitor pargyline was used as an index for 5-HT turnover in the dorsal hippocampus and raphe area. A low dose of corticosterone administered s.c. immediately after adrenalectomy significantly increased serotonin turnover in both regions over the subsequent 1 h interval. The same dose of aldosterone was ineffective, but pretreatment with aldosterone blocked the serotonin response to corticosterone in the acutely adrenalectomized rat. [3H]Corticosterone administered to adrenalectomized rats was not retained by cell nuclei of the raphe area in a limited capacity manner as occurred in the hippocampus. Pretreatment with aldosterone blocked the uptake of [3H]corticosterone in hippocampal cell nuclei. It is concluded that corticosterone triggers a serotonin response and that the specificity of the corticosterone action suggests involvement of the steroid receptor system located postsynaptically to the raphe-hippocampal serotonin projection.
Assuntos
Aldosterona/farmacologia , Tronco Encefálico/efeitos dos fármacos , Corticosterona/antagonistas & inibidores , Hipocampo/efeitos dos fármacos , Núcleos da Rafe/efeitos dos fármacos , Serotonina/fisiologia , Animais , Corticosterona/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Serotonina/metabolismoRESUMO
Following neonatal treatment with monosodium-glutamate (MSG), blood pressure in adult spontaneously hypertensive rats (SHR) was markedly lower than in control SHR, with only a small decrease in normotensive Wistar-Kyoto controls (WKY). In addition, in MSG-treated SHR an increase in pain-sensitivity was found and both strains showed increased water intake and reduced organ and body weights as compared to vehicle-treated rats.
Assuntos
Glutamatos/uso terapêutico , Hipertensão/prevenção & controle , Glutamato de Sódio/uso terapêutico , Animais , Animais Recém-Nascidos , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Dor/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Limiar Sensorial/efeitos dos fármacos , Glutamato de Sódio/farmacologia , Especificidade da EspécieRESUMO
The involvement of brain dopamine in the development of hypertension in the spontaneously hypertensive rat (SHR) was studied. Intracerebroventricular (i.c.v.) injections of 6-hydroxydopamine (6-OHDA) in young SHR caused depletion of dopamine in frontal cortex and striatum and induced an attenuation of the development of hypertension in SHR. Depletion of noradrenaline and to a lesser extent of serotonin was found as well. The ratio of DOPAC and of HVA to dopamine was increased after 6-OHDA. Pretreatment with the dopamine re-uptake inhibitor GBR-12909 inhibited the effects of 6-OHDA on both blood pressure and brain dopamine content. The effect of 6-OHDA on noradrenaline and serotonin levels were not influenced by pretreatment with GBR-12909. Electrolytic lesions in the substantia nigra delayed the rise in blood pressure in SHR. Lesions in the ventral tegmental area (VTA) were ineffective. After substantia nigra lesions depletion of dopamine was found especially in the nucleus caudatus posterior and the dorsomedial nucleus. After lesions in the VTA substantial dopamine depletion was found in the nucleus accumbens, frontal cortex, lateral septal nucleus and zona incerta. These data suggest that brain dopamine systems play a role in the development of hypertension in SHR and that especially the nigrostriatal system is important in this respect. Moreover, the present results may help to explain the attenuating effect of prehypertensive treatment with 6-OHDA on the development of hypertension.
Assuntos
Encéfalo/fisiopatologia , Dopamina/fisiologia , Hipertensão/fisiopatologia , Animais , Hidroxidopaminas , Injeções Intraventriculares , Masculino , Norepinefrina/fisiologia , Oxidopamina , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Substância Negra/fisiopatologia , Transmissão Sináptica , Tegmento Mesencefálico/fisiopatologiaRESUMO
The effects of Pro-Leu-GlyNH2 (PLG), administered i.c.v. in doses of 3.5, 35, 350 and 3500 pmol, were studied on the alpha-MPT-induced disappearance of catecholamines in microdissected rat brain nuclei. PLG, dose-dependently, increased dopamine disappearance in the nucleus caudatus and globus pallidus, whereas a decrease in dopamine disappearance was observed in the nucleus dorsomedialis. Noradrenaline disappearance was decreased in the medial septal nucleus, anterior hypothalamic area and lateral amygdala. A tendency towards an increase in noradrenaline disappearance was observed in the nucl. supraopticus. These data show that PLG has a central site of action. The effects of PLG on dopamine disappearance are comparable to those previously found with vasopressin, while the effects of PLG on noradrenaline utilization show a striking similarity with those previously obtained with oxytocin.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Hormônio Inibidor da Liberação de MSH/farmacologia , Norepinefrina/metabolismo , Animais , Injeções Intraventriculares , Sistema Límbico/metabolismo , Masculino , Metiltirosinas/farmacologia , Ratos , Ratos Endogâmicos , Transmissão Sináptica/efeitos dos fármacos , alfa-MetiltirosinaRESUMO
After the i.c.v. administration of 300 pmol ACTH-(1-24) or [Nle4,D-Phe7]alpha-MSH, a long-lasting increase in blood pressure was observed synchronously with the incidence of excessive grooming. Two structurally related peptides with no grooming behavior-inducing potency, ACTH-(7-16)-NH2 and gamma 2-MSH, in doses of 300 and 500 pmol, respectively, caused a slight and short-lasting increase in blood pressure or had no effect, respectively. When the grooming behavior-inducing effect of ACTH-(1-24) was abolished, either by the prior manipulation of central dopaminergic neurotransmission by the i.c.v. administration of the dopamine receptor antagonist, haloperidol, or, due to the occurrence of single-dose tolerance to ACTH-(1-24), the pressor response was abolished as well. These data are in support of the postulate that the incidence of grooming behavior and the elevation of blood pressure are temporally associated and indicate that the two phenomena are causally related.
Assuntos
Hormônio Adrenocorticotrópico/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Cosintropina/farmacologia , Asseio Animal/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , alfa-MSH/análogos & derivados , Hormônio Adrenocorticotrópico/administração & dosagem , Animais , Cosintropina/administração & dosagem , Haloperidol/farmacologia , Frequência Cardíaca/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Fragmentos de Peptídeos/administração & dosagem , Ratos , Ratos Wistar , alfa-MSH/farmacologiaRESUMO
A series of studies was carried out to characterize the binding properties of dopamine D1 and D2 receptors in membrane homogenates of the caudate nucleus of spontaneously hypertensive rats (SHR). Binding in SHR was studied at the age of 4 weeks when the rats were still in the prehypertensive phase, and at the age of 8 weeks, during the phase in which blood pressure is increasing dramatically; age-matched normotensive Wistar-Kyoto rats (WKY) were used as controls. Binding to dopamine D1 receptors was studied using [3H]SCH 23390. Antagonist binding of dopamine D2 receptors was performed with [3H]spiperone. At both ages no differences were found between SHR and WKY in affinity (Kd) or concentration (Bmax) of dopamine D1 and D2 receptors. Binding to the high affinity state of the dopamine D2 receptor was measured using the agonist [3H]N-n-propylnorapomorphine (NPA). No differences in Bmax or Kd were found between SHR and WKY at both ages studied, indicating that the ratio between dopamine D2 receptors in the high and in the low affinity state is not altered in spontaneous hypertension. Although the results do not reveal differences in affinities or concentrations of dopamine D1 or D2 receptors in the caudate nucleus between SHR and WKY, a role in the development of hypertension for the here described lack of receptor up-regulation in connection with our previous observation of lower release of dopamine in the caudate nucleus of SHR, cannot be excluded.
Assuntos
Núcleo Caudado/metabolismo , Dopamina/metabolismo , Hipertensão/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Animais , Hipertensão/genética , Masculino , Ensaio Radioligante , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Valores de ReferênciaRESUMO
The concentrations of noradrenaline and lopamine of 92 brain regions have been measured by a radiometric method which enabled discrimination between noradrenaline and adrenaline. Almost all brain regions investigated contained both noradrenaline and lopamine in measurable amount. However, both catecholamines appeared to be unevenly distributed. Very high dopamine concentrations were measured in the olfactory tubercle, the nucleus accumbens, the caudate nucleus and the rostral part of the medial forebrain bundle; the globus pallidus, the nucleus tractus diagonalis and the nucleus septalis lateralis were also very rich in dopamine. Outside the telencephalon the dopamine concentrations were rather low, except in the median eminence and the area tegmentalis ventralis (Tsai), an area corresponding to the A10 region. High noradrenaline concentrations were measured in most hypothalamic nuclei. Relatively high concentrations of this catecholamine were also measured in several mesencephalic (the ventral part of the central gray, the nucleus raphe dorsalis and the nucleus cuneiformis) and pontine (the locus coeruleus and the nuclei parabrachiales) regions. The highest noradrenaline concentrations in the medulla oblongata were observed in the A2 region and the nucleus commissuralis, which contained at least twice as much noradrenaline as did the more rostral part of the nucleus tractus solitarii.
Assuntos
Química Encefálica , Dopamina/análise , Norepinefrina/análise , Animais , Masculino , Bulbo/análise , Mesencéfalo/análise , Ponte/análise , Ratos , Telencéfalo/análiseRESUMO
The noradrenaline concentration and the alpha-methyl-para-tyrosine (alpha-MPT)-induced disappearance of noradrenaline were determined in several nuclei of the hypothalamus and the medulla oblongata of renal hypertensive rats (two-kidney Goldblatt hypertension). A decreased alpha-MPT-induced disappearance of noradrenaline was found in the nucleus interstitialis striae terminalis and the nucleus paraventricularis 3 days after renal artery constriction, when blood pressure was slightly, but significantly higher than that of sham operated rats. At this stage the alpha-MPT-induced disappearance of noradrenaline was enhanced in the nucleus commissuralis and the A1-region of hypertensive rats while the noradrenaline concentration in the A1-region was significantly elevated. No significant differences were found in both parameters in hypothalamic and medullary nuclei 3.5 weeks after the operation, when hypertension had fully developed. These findings are indicative of the occurrence of transient changes in the activity of noradrenergic neurons located in the medulla oblongata and projecting to the hypothalamus during the initiation of the development of two-kidney Goldblatt hypertension.
Assuntos
Hipertensão Renal/metabolismo , Hipotálamo/metabolismo , Bulbo/metabolismo , Norepinefrina/metabolismo , Animais , Masculino , Metiltirosinas/farmacologia , Ratos , Ratos EndogâmicosRESUMO
The effect of des-Tyr1-gamma-endorphin (beta-LPH62-77, DT gamma E) and des-Tyr1-alpha-endorphin (beta-LPH62-76, DT alpha E), administered intracerebroventricularly (icv) in doses of 0.01, 0.1, 1 and 10 micrograms, was studied on the alpha-methyl-p-tyrosine-(alpha-MPT) induced disappearance of catecholamines in a number of microdissected rat brain regions, which were selected on the basis of the neuroanatomy of the dopamine systems in the brain and of previous observations. A dose-dependent increase in the disappearance of dopamine in alpha-MPT-pretreated rats was observed following icv administration of DT gamma E in the nucleus interstitialis striae terminalis, the paraventricular nucleus, the anterior hypothalamic nucleus and the zona incerta. In these same brain regions a decrease in the alpha-MPT-induced disappearance of dopamine was found following the administration of DT alpha E, but only after doses of 0.01, 0.1 and 1 microgram. In none of these regions were effects observed after 10 micrograms of DT alpha E. No effects were seen on dopamine utilization in the nucleus accumbens, caudate nucleus and median eminence after any of the doses of DT gamma E or DT alpha E. The alpha-MPT-induced disappearance of noradrenaline was significantly enhanced in the anterior hypothalamic nucleus of rats treated with DT gamma E. It is concluded that DT gamma E and DT alpha E induce opposite changes in the utilization of dopamine selectively in brain regions which are predominantly innervated by neurons belonging to the intradiencephalic dopamine systems.
Assuntos
Encéfalo/metabolismo , Dopamina/metabolismo , Endorfinas/farmacologia , Metiltirosinas/farmacologia , Norepinefrina/metabolismo , Fragmentos de Peptídeos/farmacologia , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Animais , Encéfalo/efeitos dos fármacos , Relação Dose-Resposta a Droga , Cinética , Masculino , Especificidade de Órgãos , Ratos , Ratos Endogâmicos , alfa-MetiltirosinaRESUMO
In rats, the non-opioid beta-endorphin (beta E) fragment desenkephalin-gamma-endorphin (DE gamma E, beta E6-17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DE gamma E might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DE gamma E was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [3H]DA. The selective D2 receptor antagonist (-)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D2 type. DE gamma E was tested at several concentrations (10(-9)-10(-6) M) and under various experimental conditions. DE gamma E, by itself, did not affect either the electrically stimulated or the basal release of [3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DE gamma E, but this effect was present in some experiments only. It is concluded that DE gamma E does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DE gamma E does not occur at the level of this receptor.