OPPOSITE ROLE OF CCKA AND CCKB RECEPTORS IN THE MODULATION OF ENDOGENOUS ENKEPHALIN ANTIDEPRESSANT-LIKE EFFECTS

Systemic administration of RB 101, a complete inhibitor of the enkepha lin degrading enzymes, has been reported to induce naltrindole-reverse d antidepressant-like effects in the conditioned suppression of motili ty (CSM) test in mice. The selective CCKB antagonist L-365,260 also el icits the same naltrindole-blocked responses on CSM. The aim of this s tudy was therefore to investigate the possible modulation of RE 101 in duced behavioral responses by activation or blockade of CCK receptors. Thus, the effects induced by RE 101 administered alone or associated with an ineffective dose of a selective CCKB agonist (BC 264), a CCKB antagonist (L-365,260) or a CCKA antagonist (L-364,718), were evaluate d on the CSM in mice. RE 101 alone decreased the stress-induced loss o f motility, as previously reported. The antidepressant-like effect of RE 101 was potentiated by L-365,260, and suppressed by BC 264 and to a lesser extent by L-364,718. The facilitatory effect induced by L-365, 260 on RE 101 responses was blocked by the delta selective antagonist naltrindole. All these effects occurred only in shocked animals. The p resent results suggest that the activation of CCKA and CCKB receptors by endogenous CCK, could play an opposite role in the control of behav ioral responses induced by endogenous enkephalins. Delta opioid recept ors seem to be selectively involved in this interaction.