BEHAVIORAL FUNCTIONS OF NEUROPEPTIDES

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A. Microinjection of the CCK antagonist, proglumide, in the nucleus accumbens of rats, partially blocked hyperlocomotion in a darkened Digiscan activity monitor. This finding is the first evidence that endogenous CCK contributes to mesolimbic functions. B. Characterization of the ventral tegmental pharmacology of CCK found that CCK modulated DA, i.e. CCK had no effect alone, but potentiated DA-induced hypolocomotion, when microinjected into the VTA. This effect was mimicked by unsulfated CCK-8. and by CCK-4. and was not blocked by proglumide, suggesting mediation by a central-type CCK receptor subtype. A central-type CCK agonist mimicked this effect. C. Galanin is a 29-amino acid peptide which coexists with acetylcholine in the septo-hippocampal pathway of the rat. Intraventricular or intrahippocampal microinjection of nanogram doses of galanin blocked the ability of acetylcholine to reverse memory deficits on a t-maze delayed alternation task in rats lesioned in the nucleus basalis of Meynert-medial septal area. An antagonist of this inhibitory peptide is being sought as a possible approach for the treatment of some cognitive dysfunctions associated with Alzheimers disease. D. Microdialysis for neuropeptides is being developed using different plastics which allow greater passage of the large, highly charged peptides. Radioimmunoassays have detected measurable levels of cholecystokinin in the nucleus accumbens, and measurable levels of galanin in the ventral hippocampus, of anesthetized rats.