CCK-B RECEPTORS IN THE LIMBIC SYSTEM MODULATE THE ANTIDEPRESSANT-LIKEEFFECTS INDUCED BY ENDOGENOUS ENKEPHALINS

Systemic administration of RE 101, a complete inhibitor of enkephalin catabolism, has been reported to induce antidepressant-like responses in mice which were potentiated by an ineffective dose of a CCK-B antag onist. The aim of this study was to investigate the neuroanatomical su bstrate involved in the facilitatory effects induced by CCK-B antagoni sts on RE 101 behavioural responses. Thus, the CCK-B antagonist PD-134 ,308 was locally administered into different brain structures (anterio r nucleus accumbens, central amygdala and caudate nucleus) and its eff ects on the antidepressant-like response induced by systemic administr ation of RE 101 were evaluated in the conditioned suppression of motil ity (CSM) test in rats. RE 101 administered alone by the IV route decr eased the CSM in rats, as previously obtained in mice. Systemic admini stration of a non effective dose of PD-134,308 facilitated the antidep ressant-like effect induced by RE 101. Local injection of PD-134,308 i nto the anterior nucleus accumbens, the central amygdala or the caudat e nucleus did not modify CSM. The antidepressant-like effects elicited by RE 101 in this test were potentiated by PD-134,308 after microinje ction in the anterior nucleus accumbens and central amygdala, but not in the caudate nucleus. All these effects were observed only in shocke d animals. The present results suggest that the mesolimbic system, par ticularly the anterior nucleus accumbens and the central amygdala, see ms to play an important role in the interaction occurring between the endogenous CCK and opioid system in the control of behavioural respons es.