Cholecystokinin: Corelease with dopamine from nigrostriatal neurons in the cat

Halothane-anaesthetized cats were implanted with push-pull cannulae to demonstrate the in vivo release of cholecystokinin-like immunoreactivity (CCK-LI) in the substantia nigra and the ipsilateral caudate nucleus. The spontaneous and the calcium-dependent potassium-evoked release of CCK-LI were observed in both structures. In addition, the local application of tetrodotoxin (10-6 M) reduced the spontaneous release of the peptide. 6-OHDA lesions made in the substantia nigra pars compacta led to a complete destruction of nigrostriatal dopaminergic neurons. CCK-LI levels were not affected in the caudate nucleus but were reduced substantially in the substantia nigra. The activation of dopaminergic cells induced by the nigral application of alpha-methyl-para-tyrosine (10-4 M) stimulated the release of CCK-LI and dopamine in the ipsilateral caudate nucleus, whilst opposite effects were seen in the substantia nigra. Similar results were obtained when dopaminergic transmission was blocked in the caudate nucleus suggesting that the evoked release of CCK-LI by the alpha-methyl-para-tyrosine treatment originates from dopaminergic nerve terminals and not from other CCK-LI containing fibres in response to released dopamine. Dopamine (10-7 M) as well as the D1 agonist SKF 38393 (10-5 M) stimulated CCK-LI release when applied into the caudate nucleus while the D2 agonist, LY 171555 (10-6 M) slightly reduced peptide release. The local application of cholecystokinin-8 sulfate (CCK-8S) (10-8 M, for 30 min) into the substantia nigra pars compacta increased the firing rate of dopaminergic cells and stimulated the release of newly synthesized 3H-dopamine from dendrites and nerve terminals. These results suggest, but do not definitively prove, that, in the cat, CCK-LI and dopamine are coreleased from nigrostriatal mixed dopaminergic/CCK-LI neurons and that CCK-LI released from dendrites is, like dopamine, involved in the regulation of the activity of these cells.