EFFECTS OF VENTRAL HIPPOCAMPAL GALANIN ON SPATIAL-LEARNING AND ON IN-VIVO ACETYLCHOLINE-RELEASE IN THE RAT

The neuropeptide galanin coexists in the medial septum and diagonal ba nd of Broca with a population of acetylcholine neurons which project m ainly to the Ventral hippocampus. The present studies investigated the role of ventral hippocampal galanin in spatial learning in the male r at using a spatial learning task. In addition, the effects of galanin on cholinergic function were monitored by in vivo microdialysis and hi gh-performance liquid chromatography. Bilateral microinjections of gal anin (3 nmol/rat) via chronic cannulae placed into the ventral hippoca mpus (i.v.h.) produced a slight but significant impairment of acquisit ion of the spatial task, while the 1 nmol dose of galanin facilitated acquisition. The 6 nmol dose of galanin failed to affect performance. A trend for an impairment of long-term memory retention (examined seve n days after the last training session) was observed after 3 nmol of g alanin, while the 1 nmol dose facilitated retention performance. Scopo lamine (0.1 mg/kg, s.c.) caused a marked impairment of aquisition. Gal anin (3 nmol/rat) given i.v.h. failed to modify the acquisition impair ment caused by scopolamine (0.1 mg/kg, s.c.). These results suggest th at galanin given i.v.h. produces a biphasic dose-dependent effects on spatial learning. In freely moving rats, galanin (3 nmol/10 mu l) give n into the lateral ventricle (i.c.v.) did not affect basal acetylcholi ne release. In contrast, perfusion (100 min) with galanin (0.1 or 0.3 nmol/1.25 mu l/min) through the ventral hippocampal probe resulted in a reduction of basal acetylcholine release which was dose-dependent an d reversible. Galanin given i.c.v. (3 nmol/10 mu l) or through the pro be (0.3 nmol/1.25 mu l/min) attenuated the increase in acetylcholine r elease evoked by the muscarinic antagonist scopolamine (0.1 mg/kg, s.c .; 0.001 nmol/1.25 mu l/min through the probe). The galanin plus scopo lamine combinations produced a 50% lower increase in the extracellular acetylcholine concentrations than scopolamine alone. This suggests th at the mechanism(s) behind scopolamine- and galanin-induced stimulatio n of acetylcholine differ. These results indicate that ventral hippoca mpal galanin prays a role in cognition and that it has a powerful and modulatory effect on cholinergic transmission. However, the effects of exogenous galanin on spatial learning cannot be directly related to c hanges in in vivo cholinergic transmission in the ventral hippocampus. These discrepancies may relate to effects on subtypes of galanin rece ptors with different functional coupling. In addition, other hippocamp al neurotransmitter systems (e.g. noradrenergic neurons) important for cognitive functions may also be modulated by ventral hippocampal gala nin. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.