Pharmacology Biochemistry & Behavior, Vol. 13, pp. 137-139. Printed in the U.S.A. TRH on Rat Conditioned Avoidance Behavior: Interaction with Brain Catecholamines SERGIO MORA, ANTONIA G. NASELLO AND LAIS FIESCHI Laboratrrio de Medicina Experimental, Faculdade de Ci~ncias M~dicas de Santa Casa de Sro Paulo, S(7o Paulo-Brazil Received 4 October 1979 MORA, S., A. G. NASELLO AND L. FIESCHI. TRH on rat conditioned avoidance behavior: Interaction with brain catecholamines. PHARMAC. BIOCHEM. BEHAV. 13(1) 137-139, 1980.--TRH (10/xg) intracerebroventricularly injected improves the acquisition of a two-way avoidance conditioning. This effect is partially antagonized by pretreatment IP with a-methyltyrosine (60 mg/kg) or disulfiram (300 mg/kg). L-DOPA (100 mg/kg) administered IP 2 hr after a-MT partially restores the facilitatory effect of the hormone. The possible roles of brain catecholamines on the behavioral effect of TRH are analysed. Other tentative mechanisms of action are also discussed. TRH Conditioned avoidance behavior Brain catecholamines c~-Methyltyrosine Disulfiram L-DOPA AN increasing amount of experimental and clinical evidence [20] that thyrotropin-releasing-hormone (TRH) may exert di- rect effects on the central nervous system, has been pre- sented in the last few years. TRH reverses the barbiturate and ethanol narcosis in rodents [3,26]; potentiates both DOPA response in normal, hypophysectomized and thyroidectomized mice [24,25] and the behavioral changes induced by tryptophan [11] and 5-hydroxytryptophan [14]; and antagonizes the sedative and hypothermic actions of re- serpine, chlorpromazine and diazepam [17]. In a previous paper, we reported that intracerebral administration of TRH in mice increases spontaneous motility, induces tremor, ro- tational and stereotyped behavior and counteracts the effects of some antipsychotic drugs [21]. The development of sensitive and specific immunoassays for quantifying TRH, in the central nervous system of the rat, has led to the unexpected discovery that as much as 80% of total brain TRH is in extrahypothalamic structures like thalamus, brain stem, cerebral cortex and cerebellum [16]. Although no significant increase or decrease in the con- tent of any biogenic amine was observed following TRH, it has been established that dopamine (DA) content is raised 50% in mice prepared for the DOPA test [25], and that norep- inephrine (NE) turnover can be accelerated in the cerebral cortex after the administration of TRH. Behavioral evidence also supports the hypothetic interaction between TRH and CNS catecholamines [5, 20, 21]. At present the importance of an undisturbed catecholamine system for the performance of conditioned avoidance behavior is well known [7]. Differ- ent papers have shown that activation of CNS catecholamine mechanisms is involved in the acquisition of conditioned avoidance response [8,23]. In view of the evidence presented above we decided to study the effect of TRH on the acquisition of a two-way avoidance conditioning and its interactons with a-methyltyro- sine (a-MT) and disulfiram, whose effects on the bio- synthesis of catecholamines are widely known [10,19]. METHOD Subjects Albino male rats of our colony (Wistar origin), 90--140 days old, 200-250 g body weight, were used. They were housed six to an appropriate cage in a temperature regulated room (23 -+ 2°C) on a 12 hr light-dark cycle and they had food and water available ad lib. The rats were assigned ran- domly to the different control and experimental groups. Active Avoidance Conditioning As has been previously described [22], animals were training over 50 trials in a modified Warner shuttle-box. Each trial consisted of the presentation of a buzzer (con- ditioned stimulus) which after 5 sec overlapped with an elec- tric shock (1.5 mA) to the grid on the floor (unconditioned stimulus), unless the animal crossed the midline barrier as a conditioned avoidance response. Intertrial interval was 30 see. Drugs. TRH (thyrotropin-releasing hormone or pyro- Glu-His-Pro-NHz; Calbiochem) was dissolved in saline a-MT (DL-methyl-p-tyrosine; Calbiochem), L-DOPA (L- desoxyphenylalanine; Calbiochem) and disulfiram (Sigma Chem.) were suspended in a mixture of a phosphate buffer pH 6.5 and Tween 80 (10:0.2). All the drugs were adminis- ~This work was supported by Grants from FINEP-SEPLAN, Brazil, and the Servicio de Desarrollo Cientffico y Creaci6n Artfstica de la Universidad de Chile, Chile. Copyright © 1980 ANKHO International Inc.--0091-3057/80/070137-03500.80/0