Behavioral pharmacological studies on various chemicals in MAO inhibitors treated animals (Report 3). Comparison of influences of central neurotransmitter precursors on conditioned avoidance response in rats

Abstract

The current work compared the patterns of conditioned avoidance response (CAR) that followed administration of either L-DOPA,catecholamine(CA) precursor,or L-tryptophan(TRYP),5-HT precursor,to rats pretreated with tranyl-cypromine(TCP). We also aimed at an understanding of how a CNS neuronal mechanism might regulate this functional activity. l)Neither TCP+L-DOPA nor TCP+TRYP group differed in total avoidance rate from control rats,but both groups were increased 2-fold above controls in the short latency high-speed components(HSC) developed within 0-3 sec of conditioned stimuli. 2)Pre-treatment of p-chlorophenylalanine equieffectively diminished the increasing HSC of L-DOPA or TRYP. 3)Depletion of CAs by a-methyl-p-tyrosine prevented the CAR patterns. 4)Haloperidol disrupted the effects. 5)Aminooxy-acetic acid failed to affect any components of the CAR. 6)Clonidine(CL0ND) inhibited the CAR of L-DOPA,and markedly decreased the HSC of TRYP. Yohimbine abolished the CLOND-induced inhibition and recovered it to the facilitating levels elicited by both precursors. [Discussion]The results demonstrate that both precursors in the presence of TCP do produce a remarkably similar CAR changes. It is suggested that although the CAR facilitation may involve stimulation of 5-HT or dopamine receptors,there is secondary activation of a dopamine or 5-HT mechanism,respectively,since either depletion of CAs or 5-HT prevents the CAR. Our work may further support the hypothesis relating the CAR suppression after low doses of CLOND to predominant activation of a presynaptic α-adrenoceptor-mediated mechanism.