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1.
Science ; 183(4124): 539-40, 1974 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-4272136

RESUMO

The hyperthermic response of rabbits to apomorphine, a dopaminergic agonist, is abolished by prior treatment with p-chlorophenylalanine. If such 5-hydroxytryptamine (5-HT)-depleted animals are administered a peripherally acting decarboxylase inhibitor plus 5-hydroxytryptophan, central stores of 5-HT are regenerated and the hyperthermic response to apomorphine is restored in part. The effects of apomorphine in rabbits with elevated concentrations of 5-HT are not different from those in control animals. The behavioral effects of apomnorphine appear to be constant in all groups of animals tested. It is suggested that the hyperthermic effects of apomorphine in rabbits require the presence of 5-HT.


Assuntos
Apomorfina/antagonistas & inibidores , Temperatura Corporal/efeitos dos fármacos , Fenclonina/farmacologia , Animais , Química Encefálica/efeitos dos fármacos , Tronco Encefálico/análise , Carbidopa/farmacologia , Masculino , Coelhos , Serotonina/análise , Serotonina/farmacologia
2.
Science ; 164(3875): 78-9, 1969 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-5773714

RESUMO

Rabbits treated with LSD 25 exhibit characteristic signs of hyper-excitability, increased peripheral sympathetic activity, and hyperthermia. When the rabbits received prior treatment with DL-(alpha)-methyl-p-tyrosine, the excitation and sympathetic actions of LSD 25 were abolished or attenuated, but the hyperthermia was unchanged from that of the controls. Concentrations of norepinephrine in brain stems of treated rabbits were greatly decreased. The excitation of central nervous system and sympathomimetic actions of LSD 25 in the rabbit are apparently mediated by norepinephrine, whereas the hyperthermic action functions. through a nonadrenergic mechanism.


Assuntos
Comportamento Animal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Febre/induzido quimicamente , Dietilamida do Ácido Lisérgico/farmacologia , Metiltirosinas/farmacologia , Animais , Tronco Encefálico/metabolismo , Sistema Nervoso Central/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Norepinefrina/fisiologia , Coelhos , Sistema Nervoso Simpático/fisiologia
3.
Science ; 176(4037): 931-2, 1972 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-4537521

RESUMO

In rats previously treated with a monoamine oxidase inhibitor, the administration of 5-hydroxytryptophan results in increases in concentrations of 5-hydroxytryptamine in kidney, brain, and adrenal glands. When the peripheral L-aromatic amino acid decarboxylase inhibitor, L-alpha-methyl-alpha-hydrazino-beta-(3,4-dihydroxyphenyl)propionic acid (HMD) is administered prior to 5-hydroxytryptophan, the concentration of 5-hydroxytryptamine in kidneys does not rise, that of the brain increases slightly, and that of the adrenal rises markedly. This indicates that although the adrenal gland is a peripheral organ, it does not respond in the typical manner to the antidecarboxylase action of HMD. These results suggest that HMD does not gain free access into the adrenal medulla and that a possible "blood-adrenal barrier" may exist to this compound.


Assuntos
Glândulas Suprarrenais/enzimologia , Carboxiliases/antagonistas & inibidores , Metildopa/farmacologia , Propionatos/farmacologia , 5-Hidroxitriptofano/farmacologia , Glândulas Suprarrenais/análise , Animais , Química Encefálica , Catecóis/farmacologia , Feminino , Hidrazinas/administração & dosagem , Hidrazinas/farmacologia , Rim/análise , Metildopa/administração & dosagem , Pargilina/farmacologia , Ratos , Serotonina/análise , Fatores de Tempo
4.
Science ; 196(4290): 660-2, 1977 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-404705

RESUMO

Intraventricularly administered thyrotropin-releasing hormone in rabbits elicited an increase in intraluminal pressure changes, a response commonly associated with muscular activity of the colon. The response appears to be central in origin with peripheral expression relying primarily on cholinergic receptors.


Assuntos
Colo/fisiologia , Hormônio Liberador de Tireotropina/farmacologia , Animais , Atropina/farmacologia , Clorisondamina/farmacologia , Colo/inervação , Motilidade Gastrointestinal , Pressão Hidrostática , Injeções Intravenosas , Injeções Intraventriculares , Masculino , Sistema Nervoso Parassimpático/fisiologia , Coelhos , Receptores Muscarínicos/efeitos dos fármacos , Hormônio Liberador de Tireotropina/administração & dosagem , Hormônio Liberador de Tireotropina/antagonistas & inibidores
6.
Neurobiol Aging ; 8(1): 45-9, 1987.
Artigo em Inglês | MEDLINE | ID: mdl-3561665

RESUMO

Specific binding of the dopamine receptor ligand 3H-spiroperidol to cell membranes prepared from the caudate nuclei and putamens of 29 rhesus monkeys (M. mulatta), ranging in age from 2 to 22 years, was investigated. Receptor concentration (Bmax) decreased in the caudate nucleus and putamen with age at mean rates of 2.1 and 1.7% per year, respectively, whereas binding affinity (Kd) did not change significantly with age. The rate of decline in Bmax appeared to be more rapid before adulthood and in old age than during young adulthood and middle age. These data are compared with the results from similar studies of other animal species including human, rabbit, rat, and mouse. The rate of decline in striatal dopamine receptors is closely related to the rate of aging and maximal life span of the species. It may reflect both maturational and senescent processes modifying the behavior of animals as they age.


Assuntos
Envelhecimento/metabolismo , Núcleo Caudado/análise , Putamen/análise , Receptores Dopaminérgicos/análise , Animais , Feminino , Humanos , Macaca mulatta , Masculino , Camundongos , Coelhos , Ratos , Especificidade da Espécie , Espiperona/metabolismo
7.
Am J Psychiatry ; 151(11): 1694-6, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7943463

RESUMO

A low dose (0.5 mg) of thyrotropin-releasing hormone (TRH), a short-acting tripeptide with known analeptic properties, was administered to eight depressed patients 5 minutes after ECT session 3 or 4 in a double-blind, placebo-controlled crossover design. After TRH infusion the patients displayed selectively better performance on a battery of neuropsychological tests than they did after placebo infusion. Further exploration with pharmacological probes to mitigate ECT postictal cognitive deficits is warranted.


Assuntos
Transtornos Cognitivos/prevenção & controle , Transtorno Depressivo/terapia , Eletroconvulsoterapia , Hormônio Liberador de Tireotropina/administração & dosagem , Adulto , Pressão Sanguínea/efeitos dos fármacos , Transtornos Cognitivos/etiologia , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Eletroconvulsoterapia/efeitos adversos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Placebos , Hormônio Liberador de Tireotropina/uso terapêutico
8.
Neuropharmacology ; 24(2): 157-65, 1985 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-2986033

RESUMO

The regulation of receptors for thyrotropin-releasing hormone (TRH) in the central nervous system (CNS) was studied by administering the TRH analog, MK-771 to rats by three different schedules and then measuring changes in the binding of [3H](3MeHis2) TRH and behavioral responses to a challenge with MK-771. The behavioral responses monitored were wet-dog shakes, large motor movements, small motor movements and forepaw tremor. Temperature changes were also monitored. The first schedule consisted of intracerebroventricular (i.c.v.) administration of MK-771 for seven days (5 micrograms/microliter per hr) via a mini-osmotic pump. At the end of the treatment, rats showed no shaking or large motor movements typically induced by TRH, in response to a 5 mg/kg (i.p.) challenge of MK-771. Receptors were found to be 50% of control levels in the three areas of brain examined. The second schedule consisted of the administration of MK-771 (5 micrograms/2 microliters, i.c.v., once a day and 2 mg/kg, i.p., once a day). It was found that the number of receptors decreased on about the same time course as development of tolerance to wet-dog shakes and large motor movements. The third schedule consisted of the administration of MK-771 (5 micrograms/2 microliters, i.c.v.) once every 2 hr to a total of four doses. These animals eventually developed tolerance to the wet-dog shakes produced by the subsequent challenge with MK-771 and also showed a 50% decrease in receptor binding after the fourth exposure.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Temperatura Corporal/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Receptores de Superfície Celular/efeitos dos fármacos , Hormônio Liberador de Tireotropina/análogos & derivados , Animais , Depressão Química , Tolerância a Medicamentos , Injeções Intraventriculares , Masculino , Ratos , Ratos Endogâmicos , Receptores do Hormônio Liberador da Tireotropina , Tiazolidinas , Hormônio Liberador de Tireotropina/farmacologia
9.
Neuropharmacology ; 28(5): 481-6, 1989 May.
Artigo em Inglês | MEDLINE | ID: mdl-2566949

RESUMO

Fentanyl (20 micrograms/kg i.p.), administered to naltrexone-pretreated, pentobarbital-anesthetized rats, produced a shortening of the duration of narcosis. This analeptic effect was blocked by atropine, but not by methylatropine, indicating that a central cholinergic mechanism was involved. Fentanyl also increased sodium-dependent high affinity uptake of choline activity in the hippocampus and cortex that had been depressed by the barbiturate. Injection of 0.8 ng of fentanyl into the pontis oralis in the pontine reticular formation also produced analepsis in naltrexone-pretreated, pentobarbitalized rats. Hippocampal EEG recordings also showed the appearance of cholinergically-mediated theta activity, which was indicative of arousal activity in the hippocampus. These results suggest that fentanyl, in addition to possessing potent opiate activity, also activates a nonopioid-mediated central cholinergic arousal system.


Assuntos
Estimulantes do Sistema Nervoso Central , Eletroencefalografia , Fentanila/farmacologia , Sistema Nervoso Parassimpático/fisiologia , Anestesia , Animais , Atropina/farmacologia , Encéfalo , Colina/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Injeções , Masculino , Naltrexona/farmacologia , Pentobarbital/antagonistas & inibidores , Ratos , Ratos Endogâmicos , Sono/efeitos dos fármacos , Estimulação Química
10.
Neuropharmacology ; 22(10): 1183-6, 1983 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-6646353

RESUMO

Morphine was administered by the intracerebroventricular (i.c.v.) route to pentobarbital-anesthetized rabbits. Small doses of morphine (less than 150 micrograms) potentiated, but larger doses (greater than 250 micrograms) shortened, the duration of anesthesia. In naltrexone-pretreated animals, all doses of morphine employed acted only as an analeptic. Atropine, but not atropine methylbromide, blocked the analeptic effect of morphine, indicating that a central cholinergic mechanism was involved in this response. Tolerance to the analeptic effect was not evident. These results suggest that morphine exerts an arousal action which is usually masked by the dominant narcotic properties, but which becomes evident when administered intracerebroventricularly or in the presence of naltrexone.


Assuntos
Anestesia , Morfina/farmacologia , Pentobarbital/antagonistas & inibidores , Animais , Atropina/farmacologia , Comportamento Animal/efeitos dos fármacos , Eletroencefalografia , Masculino , Naloxona/farmacologia , Naltrexona/farmacologia , Coelhos , Convulsões/fisiopatologia
11.
Neuropharmacology ; 23(9): 1109-12, 1984 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-6514146

RESUMO

In previous research, we discovered two DA-related thermoregulatory mechanisms in the rat: a haloperidol-sensitive, hypothermia-inducing mechanism and a haloperidol-nonsensitive, hyperthermia-inducing mechanism. The latter mechanism must also involve serotonin, since its activity can be blocked by serotonin antagonists. We have now found that the responsiveness of these mechanisms to apomorphine could be selectively affected by acute pretreatments with apomorphine, haloperidol and ethanol. The hypothermia-inducing mechanism was supersensitized by pretreatment with either haloperidol (0.25 mg/kg, administered 5 days earlier) or ethanol (3 g/kg, 15 h), but was not affected by pretreatment with apomorphine (1 mg/kg, 15h). In contrast, the hyperthermia-inducing mechanism was supersensitized and desensitized by similar pretreatments with apomorphine and ethanol, respectively, but was not affected by pretreatment with haloperidol.


Assuntos
Apomorfina/farmacologia , Regulação da Temperatura Corporal/efeitos dos fármacos , Etanol/farmacologia , Haloperidol/farmacologia , Animais , Masculino , Ratos , Ratos Endogâmicos , Fatores de Tempo
12.
Neuropharmacology ; 32(5): 487-92, 1993 May.
Artigo em Inglês | MEDLINE | ID: mdl-8100623

RESUMO

The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.


Assuntos
Nível de Alerta/efeitos dos fármacos , Benzazepinas/farmacologia , Cocaína/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Receptores de Dopamina D1/antagonistas & inibidores , Salicilamidas/farmacologia , Análise de Variância , Animais , Estimulantes do Sistema Nervoso Central/farmacologia , Interações Medicamentosas , Eletroencefalografia/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Masculino , Coelhos , Racloprida , Fatores de Tempo
13.
Psychopharmacology (Berl) ; 82(4): 335-7, 1984.
Artigo em Inglês | MEDLINE | ID: mdl-6427825

RESUMO

Apomorphine-induced hypothermia was studied in rats pretreated with a dose of apomorphine (mg/kg, IP), haloperidol (0.25 mg/kg, IP), ethanol (3 g/kg, PO), or apomorphine + ethanol. Pretreatment with apomorphine attenuated the hypothermic response, pretreatment with either haloperidol or ethanol potentiated it, and pretreatment with apomorphine together with ethanol did not alter it. These data show that an acute treatment with a dopaminergic drug can alter the responsiveness of the dopaminergic thermoregulatory system, and also that ethanol has an inhibitory effect on the dopamine mechanism.


Assuntos
Apomorfina/farmacologia , Temperatura Corporal/efeitos dos fármacos , Etanol/farmacologia , Haloperidol/farmacologia , Animais , Interações Medicamentosas , Masculino , Ratos , Ratos Endogâmicos , Fatores de Tempo
14.
Psychopharmacology (Berl) ; 49(1): 57-62, 1976 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-822448

RESUMO

Thyrotropin releasing hormone (TRH) administered via the intracerebroventricular (icv) route in doses ranging between 0.1 and 100 mug decreased the duration of pentobarbital-induced narcosis in rabbits. Antagonism of narcosis occurred whether TRH was administered before or after the barbiturate. TRH doses above 10 mug produced, in addition, behavioral excitation and hyperthermia. The antagonism of phenobarbital-induced narcosis was not as profound; animals were aroused only for a short period of time, after which the narcotized state returned. However, TRH exerted a prolonged antagonism or reversal of the phenobarbital-induced hypothermia. The central nervous system depression and analgesia produced by morphine were unaffected by TRH, but hypothermia and respiratory depression were reversed. TRH may represent an arousal factor in mammalian brain.


Assuntos
Nível de Alerta/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Animais , Temperatura Corporal/efeitos dos fármacos , Injeções Intraventriculares , Masculino , Morfina/antagonistas & inibidores , Pentobarbital/antagonistas & inibidores , Fenobarbital/antagonistas & inibidores , Coelhos , Sono/efeitos dos fármacos
15.
Psychopharmacology (Berl) ; 75(4): 388-90, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-6122233

RESUMO

Apomorphine (AP)-elicited sterotypic behavior and striatal 3H-spiroperidol binding sites were studied in rats given 3 weeks of chronic treatment with one of the following neuroleptic drugs: zotepine (10 or 20 mg/kg/day IP); thioridazine (10 or 20 mg/kg/day IP); haloperidol (2 or 5 mg/kg/day IP). On days 10-12 after the chronic neuroleptic treatment, enhancement of AP-elicited stereotypy was seen in the high- and low-dose haloperidol-treated, as well as in the high-dose thioridazine and zotepine-treated rats when compared to that of saline-injected controls. No significant change in the response to AP was found in the low-dose thioridazine and zotepine-treated animals. Significant increases in the concentration of striatal 3H-spiroperidol binding sites were seen after treatment with all three neuroleptics, both high and low doses. A positive correlation was found between AP-elicited stereotypy and the concentration of striatal 3H-spiroperidol binding sites in the haloperidol-treated and control rats. However, no such correlation was seen after chronic thioridazine and zotepine treatments.


Assuntos
Antipsicóticos/farmacologia , Butirofenonas/metabolismo , Corpo Estriado/metabolismo , Espiperona/metabolismo , Comportamento Estereotipado/efeitos dos fármacos , Animais , Apomorfina/farmacologia , Sítios de Ligação/efeitos dos fármacos , Dibenzotiepinas/farmacologia , Interações Medicamentosas , Haloperidol/farmacologia , Humanos , Masculino , Ratos , Ratos Endogâmicos , Tioridazina/farmacologia
16.
Psychopharmacology (Berl) ; 88(3): 354-61, 1986.
Artigo em Inglês | MEDLINE | ID: mdl-3083456

RESUMO

In a series of experiments, we investigated the effects of pulsed low-level microwave irradiation on amphetamine-induced hyperthermia in the rat. Rats were irradiated in a 2,450-MHz cylindrical waveguide exposure system at 1 mW/cm2, 2 mus pulses, 500 pps, average SAR of 0.6 W/kg. Acute (45 min) exposure to microwaves attenuated amphetamine-induced hyperthermia. This effect was blocked by pretreatment of the animals with the narcotic antagonist naloxone. In another experiment, rats were subjected to ten daily sessions of microwave exposure (45 min/session). On day 11, amphetamine-induced hyperthermia was studied in the animals immediately after a session of either microwave or sham exposure. Similar to the acute effect, amphetamine-induced hyperthermia was attenuated in rats irradiated with microwaves (unconditioned effect). In the sham-irradiated animals we observed a potentiation of the amphetamine-induced hyperthermia, which was a conditioned effect of microwaves. Thus, the conditioned effect (potentiation) was opposite in direction to the unconditioned effect (attenuation). No tolerance developed to the unconditioned effect after subchronic exposure. Furthermore, both conditioned and unconditioned effects of microwaves on amphetamine-induced hyperthermia could be blocked by treatment with naloxone. These data suggest that microwave irradiation may activate endogenous opioids, which in turn alter the actions of psychoactive drugs, and the effect of microwaves on drug action can be classically conditioned.


Assuntos
Anfetamina/farmacologia , Temperatura Corporal/efeitos da radiação , Condicionamento Clássico/efeitos da radiação , Micro-Ondas , Naloxona/farmacologia , Anfetamina/antagonistas & inibidores , Animais , Temperatura Corporal/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Masculino , Ratos , Ratos Endogâmicos
17.
Psychopharmacology (Berl) ; 74(1): 13-6, 1981.
Artigo em Inglês | MEDLINE | ID: mdl-6115440

RESUMO

In the rat, the antimuscarinics atropine and scopolamine failed to block the reduction in pentobarbital-induced sleep time produced by either thyrotropin-releasing hormone (TRH) or MK-771 (a TRH analog). Previous reports have indicated that the marked analeptic effect produced by TRH is antagonized by such agents. It is not clear at this time whether the difference between our findings and these previous studies indicates a reduced sensitivity of cholinergic receptors in the rat to muscarinic blockade, a different neurochemical mechanism of action of TRH in the rat, or other unknown factors.


Assuntos
Estimulantes do Sistema Nervoso Central/antagonistas & inibidores , Parassimpatolíticos/farmacologia , Receptores Colinérgicos/efeitos dos fármacos , Receptores Muscarínicos/efeitos dos fármacos , Hormônio Liberador de Tireotropina/análogos & derivados , Hormônio Liberador de Tireotropina/antagonistas & inibidores , Animais , Hipocampo/efeitos dos fármacos , Masculino , Camundongos , Fenobarbital/farmacologia , Ratos , Especificidade da Espécie , Tiazolidinas
18.
Psychopharmacology (Berl) ; 61(1): 1-9, 1979 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-108711

RESUMO

Acute oral administration of ethanol increased the rate of depletion of dopamine in the striata of rats injected with alpha-methyl-p-tyrosine. This effect was eliminated by pretreatment with atropine or by lesioning of the striato-nigral tract. Ethanol also attenuated the inhibitory effect of apomorphine on turnover of striatal dopamine. Unilateral injection of ethanol into the neostriatum of rats followed by intraperitoneal injection of either apomorphine or amphetamine elicited marked ipsilateral head-to-tail body turning. This turning was blocked by pretreatment with haloperidol. Chronic intubation of ethanol to rats enhanced contralateral body turning elicited by unilateral intrastriatal injection of dopamine. Injection of 6-hydroxydopamine into the substantia nigra led to denervation supersensitivity of dopaminergic functions in the neostriatum. This effect was not seen in rats that were given ethanol postinjection of 6-hydroxydopamine. These results suggested that ethanol has an inhibitory effect on the nigrostriatal dopaminergic system.


Assuntos
Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Etanol/farmacologia , Animais , Corpo Estriado/metabolismo , Corpo Estriado/fisiologia , Denervação , Dopamina/fisiologia , Humanos , Hidroxidopaminas/farmacologia , Cinética , Masculino , Ratos , Comportamento Estereotipado/efeitos dos fármacos , Substância Negra/fisiologia
19.
Peptides ; 11(5): 1021-5, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-1980941

RESUMO

Intracerebroventricular (ICV) microinjection of arginine vasopressin (AVP) to pentobarbital-anesthetized rats produced shortening of the duration of narcosis. This analeptic effect was blocked by atropine, indicating the central cholinergic nature of the response. AVP also increased hippocampal sodium-dependent high affinity choline uptake activity that had been depressed by the barbiturate. The AVP analeptic effect was blocked by pretreatment with a V-1 (vasopressor), but not a V-2 (antidiuretic), vasopressin receptor antagonist. These results suggest that ICV AVP produces its analeptic effect by interacting with central V-1 receptors to activate a hippocampal cholinergic arousal system. The cholinergic arousal effect may be a factor in the memory enhancing property of AVP.


Assuntos
Arginina Vasopressina/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Hipocampo/efeitos dos fármacos , Pentobarbital/antagonistas & inibidores , Receptores de Angiotensina/efeitos dos fármacos , Acetilcolina/fisiologia , Animais , Arginina Vasopressina/administração & dosagem , Arginina Vasopressina/antagonistas & inibidores , Nível de Alerta/efeitos dos fármacos , Atropina/farmacologia , Estimulantes do Sistema Nervoso Central/antagonistas & inibidores , Hipocampo/metabolismo , Injeções Intraventriculares , Masculino , Memória/efeitos dos fármacos , Microinjeções , Ratos , Ratos Endogâmicos , Receptores de Angiotensina/fisiologia , Receptores de Vasopressinas
20.
Peptides ; 10(1): 121-4, 1989.
Artigo em Inglês | MEDLINE | ID: mdl-2501767

RESUMO

Microinjection of ibotenic acid into medial septum of rats decreased choline acetyltransferase (CAT) and high-affinity choline uptake (HACU) activities in hippocampus and retarded the learning of a spatial memory task in the radial-arm maze. Administration of MK-771, a stable TRH analog, to such animals restored HACU activity in hippocampus to normal levels. Daily treatment of rats with MK-771 prior to maze running also restored the animals' learning ability. MK-771 did not enhance hippocampal HACU activity or maze performance in sham-lesioned rats. These results suggest that MK-771 reversed the ibotenic acid-induced memory deficit by restoring septohippocampal cholinergic function. MK-771 and other TRH analogs may represent novel agents for improving memory deficits produced by cholinergic insufficiency in Alzheimer's disease.


Assuntos
Antidepressivos/farmacologia , Colina O-Acetiltransferase/metabolismo , Hipocampo/fisiologia , Aprendizagem/efeitos dos fármacos , Hormônio Liberador de Tireotropina/análogos & derivados , Animais , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Ácido Ibotênico/farmacologia , Masculino , Ratos , Ratos Endogâmicos , Valores de Referência , Tiazolidinas , Hormônio Liberador de Tireotropina/farmacologia
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