COADMINISTRATION OF GALANIN ANTAGONIST M40 WITH A MUSCARINIC M-1 AGONIST IMPROVES DELAYED NONMATCHING TO POSITION CHOICE ACCURACY IN RATS WITH CHOLINERGIC LESIONS

The neuropeptide galanin is overexpressed in the basal forebrain in Al zheimer's disease (AD). In rats, galanin inhibits evoked hippocampal a cetylcholine release and impairs performance on several memory tasks, including delayed nonmatching to position (DNMTP). Galanin(1-13)-Pro(2 )-(Ala-Leu)(2)-Ala-NH2 (M40), a peptidergic galanin receptor ligand, h as been shown to block galanin-induced impairment on DNMTP in rats. M4 0 injected alone, however, does not improve DNMTP choice accuracy defi cits in rats with selective cholinergic immunotoxic lesions of the bas al forebrain. The present experiments used a strategy of combining M40 with an M-1 cholinergic agonist in rats lesioned with the cholinergic immunotoxin (192)IgG-saporin. Coadministration of intraventricular M4 0 with intraperitoneal iadiazol-4-yl)-1,2,5,6-tetrahydro-1-methylpyrid ine (TZTP), an M-1 agonist, improved choice accuracy significantly mor e than a threshold dose of TZTP alone. These results suggest that a ga lanin antagonist may enhance the efficacy of cholinergic treatments fo r the cognitive deficits of AD.