Differential effects of the neuropeptide galanin on striatal acetylcholine release in anaesthetized and awake rats.

1. In the present study the mechanisms were examined by which the neuropeptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in enflurane anaesthetized and in freely moving male rats by use of in vivo microdialysis and high performance liquid chromatography. 2. The perfusion of galanin through the microdialysis probe (0.3 nmol microl(-1), flow rate: 2 microl min(-1)) caused a statistically significant increase in the basal striatal ACh levels in anaesthetized but a decrease in awake animals. No significant effect was revealed after a low dose (0.1 nmol microl(-1), flow rate: 2 microl min(-1)) of galanin perfusion. Both the stimulating and inhibitory effects of galanin on basal ACh release were reversible. 3. The muscarinic antagonist scopolamine (0.1 mg kg(-1), subcutaneously (s.c.)) caused a significant increase in ACh release in both anaesthetized and awake animals. 4. The combination of galanin plus scopolamine attenuated the stimulant effect on ACh release caused by scopolamine alone in awake animals. 5. The putative galanin receptor antagonist M35 at 0.3 nmol microl(-1) but not at 0.1 nmol microl(-1) caused a significant reduction (20%) in ACh release, supporting the view that M35 at higher concentrations behaves as a partial agonist at the galanin receptor. When M35 (0.1 nmol microl(-1)) was co-infused with galanin (0.3 nmol microl(-1)) the galanin-evoked decrease in ACh release was completely blocked. 6. Taken together, these results indicate that galanin affects basal ACh release via stimulation of galanin receptors within the striatum. The mechanism involved is dependent on the anaesthesia procedure which may act via enhancement of gamma-aminobutyric acidA (GABA(A)) mediated transmission within striatal and/or output neurones. In addition, anaesthesia may also decrease the activity of glutamatergic striatal afferents. The results with M35 indicate that the role of galanin perfused in striatum is permissive in the normal rat. Furthermore, galanin is a potent inhibitory modulator of basal ACh release also in the striatum, as recently was shown in the ventral hippocampus in awake animals.