Intraventricular galanin modulates a 5‐HT_1A receptor‐mediated behavioural response in the rat

Abstract

The present studies have examined whether the neuropeptide galanin can modulate brain serotoninergic (5-HT) neurotransmission in vivo and, particularly, 5-HT1A receptor-mediated transmission. For that purpose, we studied the ability of galanin (given bilaterally into the lateral ventricle, i.c.v.) to modify the impairment of passive avoidance retention induced by the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propyloamino)tetralin (8-OH-DPAT) when injected prior to training. This impairment appears to be mainly related to activation of 5-HT1A receptors in the CNS. Galanin dose-dependently (significant at 3.0 nmol/rat) attenuated the passive avoidance impairment (examined 24 h after training) induced by the 0.2 mg/kg dose of 8-OH-DPAT. This 8-OH-DPAT dose produced signs of the 5-HT syndrome indicating a postsynaptic 5-HT1A receptor activation. Furthermore, both the impairment of passive avoidance and the 5-HT syndrome were completely blocked by the 5-HT1A receptor antagonist WAY 100635 (0.1 mg/kg). Galanin (0.3 or 3.0 nmol) or WAY 100635 (0.1 mg/kg) failed by themselves to affect passive avoidance retention. 8-OH-DPAT given at a low dose 0.03 mg/kg, which presumably stimulates somatodendritic 5-HT1A autoreceptors in vivo, did not alter passive avoidance retention or induce any visually detectable signs of the 5-HT syndrome. Galanin (0.3 or 3.0 nmol) given i.c.v. in combination with the 0.03 mg/kg dose of 8-OH-DPAT, did not modify passive avoidance. The immunohistochemical study of the distribution of i.c.v. administered galanin (10 min after infusion) showed a strong diffuse labelling in the periventricular zone (100-200 microm) of the lateral ventricle. Furthermore, in the dorsal and ventral hippocampus galanin-immunoreactive nerve cells appeared both in the dentate gyrus and the CA1, CA2 and CA3 layers of the hippocampus. In the septum only endogenous fibres could be seen while in the caudal amygdala also galanin-immunoreactive nerve cells were visualized far away from the labelled periventricular zone. At the level of the dorsal raphe nucleus a thin periventricular zone of galanin immunoreactivity was seen but no labelling of cells. These results suggest that galanin can modulate postsynaptic 5-HT1A receptor transmission in vivo in discrete cell populations in forebrain regions such as the dorsal and ventral hippocampus and parts of the amygdala. The indication that galanin administered intracerebroventrically may be taken up in certain populations of nerve terminals in the periventricular zone for retrograde transport suggests that this peptide may also affect intracellular events.

Differential Role of Galanin Receptors in the Regulation of Depression-Like Behavior and Monoamine/Stress-Related Genes at the Cell Body Level

“…Electrophysiological, behavioral, and neurochemical studies have shown that galanin exerts modulatory (mainly inhibitory) effects on both the noradrenergic and serotonergic systems (Seutin et al, 1989;Sevcik et al, 1993;Pieribone et al, 1995;Xu et al, 1998c;Razani et al, 2001;Kehr et al, 2002;see Ö gren et al, 2006). Moreover, in vivo galanin can modulate 5-HT 1A preand postsynaptic receptor functions in an antagonistic manner (see Fuxe et al, 1998;Misane et al, 1998; The action of galanin is mediated via three G proteincoupled receptors, GalR1-GalR3 (see Branchek et al, 2000), which are expressed in the LC, DR, and their projection areas (Xu et al, 1998b, c;O'Donnell et al, 1999;Burazin et al, 2000;Larm et al, 2003;Hawes and Picciotto, 2004;Hawes et al, 2005;Swanson et al, 2005). Among these receptors, GalR1 and GalR3 mainly activate G i/o types of G proteins mediating inhibitory actions of galanin (Habert-Ortoli et al, 1994;Burgevin et al, 1995;Parker et al, 1995;see Branchek et al, 2000).…”

Ethanol-related alterations in gene expression patterns in the developing murine hippocampus

“…Gal is an inhibitory neuropeptide that is widely expressed in the central and peripheral nervous systems in vertebrates [29]. It co-exists within neurons with several small molecular classical neurotransmitters [30] and exerts strong inhibitory actions on synaptic transmission by reducing the release of neurotransmitters [31,32]. It has been previously reported that Gal shows distinct up-regulation after pathological disturbance within the nervous system, such as peripheral nerve injury [33].…”

Galanin Is a Potent In Vivo Modulator of Mesencephalic Serotonergic Neurotransmission

“…The deficit in passive avoidance by systemic 8-OH-DPAT appears to be related to activation of postsynaptic 5-HT 1A receptors in the limbic forebrain, e.g. the hippocampus (Carli et al 1993;Misane et al 1998). However, the reduction in the postsynaptic 5-HT 1A receptor response after i.c.v.…”