Improvement by dynorphin A (1-13) of galanin-induced impairment of memory accompanied by blockade of reductions in acetylcholine release in rats.

1 Human galanin (0.32 nmol per rat, i.c.v.), an endogenous neuropeptide, administered 30 min before acquisition or retention trials, significantly impaired the acquisition of learning and recall of memory in a step-through type passive avoidance performance. 2 The role of dynorphin A (1–13) in learning and memory is controversial. Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) administered 5 min before galanin injection, completely antagonized these impairments. 3 Galanin significantly decreased acetylcholine release in the hippocampus 40 to 120 min after injection as determined by in vivo brain microdialysis. This peptide also decreased acetylcholine release, albeit to a lesser extent, from the frontal cortex. 4 Dynorphin A (1–13) (0.5 nmol per rat, i.c.v.) 5 min before galanin injection, completely blocked the decrease in extracellular acetylcholine concentration induced by galanin. 5 These antagonistic effects of dynorphin A (1–13) were abolished by treatment with nor-binaltorphimine (5.44 nmol per rat, i.c.v.), a selective κ-opioid receptor antagonist, 5 min before dynorphin A (1–13). 6 Dynorphin A (1–13) (0.5 nmol) itself had no effect on learning and memory and on the acetylcholine concentration in the hippocampus or the frontal cortex in normal rats. 7 These results suggest that the neuropeptide dynorphin A (1–13) ameliorates the galanin-induced impairment of learning and memory accompanied by abolition of reductions in acetylcholine release via κ-opioid receptors.