Using extracellular single unit recording techniques, we have examined the effects of stress and pharmacological agents which either alleviate or mimic the effects of stress on individual neurons in the rat substantia nigra (SN). Specifically, learned helplessness induced by uncontrollable stressful shocks results in a supersensitivity to gamma-amino butyric acid (GABA) agonists while shocks which are controllable do not produce GABAergic supersensitivity. The anxiogenic benzodiazepine (BZ) receptor ligand, beta-carboline carboxylate ethyl ester (BetaCCE) increases the activity of neurons in the SN zona reticulata (ZR) but had no effect on noradrenergic neurons in the locus coeruleus. Caffeine also mimics many of the effects of beta-CCE in the SN but its actions are not reversed by the specific BZ antagonist Ro-15-1788 as are those of beta-CCE. Furthermore, the recently isolated putative endogenous peptide ligand for the BZ receptor, diazepam binding inhibitor (DBI), excites ZR neurons. These effects could not be reversed by Ro-15-1788 suggesting that this peptide may not act through the BZ receptor. We have continued our studies on the interactions between endogenously occurring neuropeptides and classical neurotransmitters. All varieties of CCK-like peptides which bind to brain CCK receptors also potentiate DA in those areas where CCK and DA coexist while those CCK-like peptides which do not bind to this receptor are ineffectual in facilitating DA inhibition. The putative cholecystokinin (CCK) antagonists, proglumide and benzotript, were found to weakly block CCK in proportion to their potency at central CCK receptors. Dynorphin (DYN) appears to modulate the response of SNZR neurons to GABA. Finally, we have examined the effects to cholinergic agents in the SN. Nicotinic agents appear to activate DA neurons in the SN through a central mechanism.
