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

Abstract

1 In the present study the mechanisms were examined by which the neuropeptide galanin modulates the extracellular concentrations of striatal acetylcholine (ACh) in en¯urane 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 ml 71 ,¯ow rate: 2 ml min 71 ) caused a statistically signi®cant increase in the basal striatal ACh levels in anaesthetized but a decrease in awake animals. No signi®cant eect was revealed after a low dose (0.1 nmol ml 71 ,¯ow rate: 2 ml min 71 ) of galanin perfusion. Both the stimulating and inhibitory eects of galanin on basal ACh release were reversible. 3 The muscarinic antagonist scopolamine (0.1 mg kg 71 , subcutaneously (s.c.)) caused a signi®cant increase in ACh release in both anaesthetized and awake animals. 4 The combination of galanin plus scopolamine attenuated the stimulant eect on ACh release caused by scopolamine alone in awake animals. 5 The putative galanin receptor antagonist M35 at 0.3 nmol ml 71 but not at 0.1 nmol ml 71 caused a signi®cant 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 ml 71 ) was co-infused with galanin (0.3 nmol ml 71) the galanin-evoked decrease in ACh release was completely blocked. 6 Taken together, these results indicate that galanin aects 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 g-aminobutyric acid A (GABA A ) mediated transmission within striatal and/or output neurones. In addition, anaesthesia may also decrease the activity of glutamatergic striatal aerents. 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.

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

“…Since, M35 has about the same affinity for both GalR1 (Ki ϭ 0.3 nM) and GalR2 (Ki ϭ 0.6 nM) receptor subtypes, it is not possible to link the blockade of the galanin effect to any specific galanin receptor subtype in the DRN. Administration of M35 itself caused a slight but significant reduction of basal extracellular 5-HT at 120 min, which is in agreement both with in vitro data in insulinoma cell lines (Kask et al 1995) and in vivo data showing a partial agonistic mode of action of M35 (Antoniou et al 1997). The temporal increase of the 5-HT levels at 20-40 min following galanin administration in the M35 pretreated group could be explained by an increased sensitivity to the acute stress caused during the insertion of the i.c.v.…”

Selective 5-HT1A Antagonists WAY 100635 and NAD-299 Attenuate the Impairment of Passive Avoidance Caused by Scopolamine in the Rat

“…The interval between the s.c. administration of scopolamine and training in this study was 40 min, which is longer than in most previous PA studies (varying usually between 5 and 30 min) (Bammer, 1982). The choice of this time interval was based on in vivo microdialysis studies, in which s.c. scopolamine produced an increase in the ACh levels in the ventral hippocampus with a peak effect after 40-60 min (Antoniou et al, 1997;Ö gren et al, 1996;Toide and Arima, 1989).…”

Galanin Protects Against Behavioral and Neurochemical Correlates of Opiate Reward

“…Whereas mRNA levels for galanin receptors are low in the NAc, galanin receptor binding is quite prominent (Burgevin et al, 1995;Gustafson et al, 1996;Hawes and Picciotto, 2004;Kolakowski et al, 1998;Waters and Krause, 2000), indicating that localization of galanin receptors on DA terminals might regulate DA release. Galanin is also known to be a potent inhibitory modulator of basal acetylcholine (ACh) release in the striatum (Antoniou et al, 1997) and it has been demonstrated that M1-muscarinic receptors and high-affinity nicotinic receptors regulate the secondary rewarding effects of cues paired with a primary reinforcer such as morphine (Brunzell et al, 2006;Carrigan and Dykstra, 2007). Lack of galanin may therefore increase availability of ACh, thus increasing the sensitivity of GKO mice to opiates.…”

“…Lack of galanin may therefore increase availability of ACh, thus increasing the sensitivity of GKO mice to opiates. Finally, galanin has also been shown to decrease GABA release in the cortex and striatum (Antoniou et al, 1997;Ellis and Davies, 1994), potentially increasing excitability in these brain areas and contributing to morphine's behavioral effects. The effects of galanin on morphine-related behaviors may therefore modulate reward pathways through multiple neurotransmitter systems.…”