DIFFERENTIAL-EFFECTS OF THE NEUROPEPTIDE GALANIN ON STRIATAL ACETYLCHOLINE-RELEASE IN ANESTHETIZED AND AWAKE RATS

1 In the present study the mechanisms were examined by which the neuro peptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in enflurane anaesthetized and in freely moving m ale rats by use of in vivo microdialysis and high performance liquid c hromatography. 2 The perfusion of galanin through the microdialysis pr obe (0.3 nmol mu l(-1), flow rate: 2 mu l min(-1)) caused a statistica lly significant increase in the basal striatal ACh levels in anaesthet ized but a decrease in awake animals. No significant effect was reveal ed after a low dose (0.1 nmol mu l(-1). how rate: 2 mu l min(-1)) of g alanin perfusion. Both the stimulating and inhibitory effects of galan in on basal ACh release were reversible. 3 The muscarinic antagonist s copolamine (0.1 mg kg(-1), subcutaneously (s.c.)) caused a significant increase in ACh release in both anaesthetized and awake animals. 4 Th e combination of galanin plus scopolamine attenuated the stimulant eff ect on ACh release caused by scopolamine alone in awake animals. 5 The putative galanin receptor antagonist M35 at 0.3 nmol mu l(-1) but not at 0.1 nmol mu l(-1) caused a significant reduction (20%) in ACh rele ase? supporting the view that M35 at higher concentrations behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol mu l(-1) ) was co-infused with galanin (0.3 nmol mu l(-1)) the galanin-evoked d ecrease in ACh release was completely blocked. 6 Taken together, these results indicate that galanin affects basal ACh release via stimulati on of galanin receptors within the striatum. The mechanism involved is dependent on the anaesthesia procedure which may act via enhancement of gamma-aminobutyric acid(A) (GABA(A)) mediated transmission within s triatal and/or output neurones. In addition, anaesthesia may also decr ease the activity of glutamatergic striatal afferents. The results wit h M35 indicate that the role of galanin perfused in striatum is permis sive in the normal rat. Furthermore. galanin is a potent inhibitory mo dulator of basal ACh release also in the striatum, as recently was sho wn in the ventral hippocampus in awake animals.