RESUMO
An electrobrainshock (EBS)-induced memory retrieval deficit was produced in normal and hypophysectomized mice. In normal mice, thyrotropin-releasing hormone (TRH) (0.1 to 30 mg/kg) protected against this EBS disruption of memory after intraperitoneal but not oral (1.0 to 100 mg/kg) administration. In hypophysectomized mice, TRH (0.3 and 3.0 mg/kg) also protected against the retrieval deficit induced by EBS. The memory protection afforded by TRH was unrelated to its ability to elevate plasma levels of triiodothyronine (T3) and thyroxine (T4), nor was TRH's memory protection mediated through an anticonvulsive mechanism. These results support the notion that TRH may play an important role in memory modulation and may have therapeutic value in certain disease states in humans.
Assuntos
Glândulas Endócrinas/efeitos dos fármacos , Memória/efeitos dos fármacos , Hormônio Liberador de Tireotropina/farmacologia , Administração Oral , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletrochoque , Hipofisectomia , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Hormônio Liberador de Tireotropina/administração & dosagem , Tiroxina/sangue , Tri-Iodotironina/sangueRESUMO
Ro 22-1319, a novel pyrroloisoquinoline compound, was identified as a potential antipsychotic agent in a rat discrete avoidance procedure that is highly specific for such agents. Results in this test are highly correlated with the clinical potency of all types of antipsychotic agents. The avoidance-blocking potency of Ro 22-1319 (0.7 mg/kg) in this procedure approached that of haloperidol (0.4 mg/kg) and was 7- and 12-times greater than that of chlorpromazine and clozapine, respectively. Ro 22-1319 exhibited similar high potency in other rat and monkey avoidance procedures, rat motor activity, and antagonism of apomorphine emesis in dogs. High potency and antipsychotic-like activity have been demonstrated in monkey EEG and in an in vivo 3H-spiroperidol binding assay. Although studies of amphetamine antagonism in rats indicate antidopaminergic activity at nigrostriatal sites, Ro 22-1319 exhibited relatively weaker cataleptogenic and antistereotypic activity than haloperidol, and had minimal activity in a rat chronic stereotypy model of receptor supersensitivity. This profile suggests that Ro 22-1319 is an efficacious antipsychotic compound, almost as potent as haloperidol, with fewer or less intense extrapyramidal effects and low potential for tardive dyskinesia.
