Effect of 5-HT1A receptor ligands on Fos-like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission

Abstract

This study investigated the effects of 8-OH-DPAT and various other 5-HT(1A) receptor agonists on brain noradrenergic transmission using Fos-like immunoreactivity (Fos-LI) as a marker of neural activation. Administration of 8-OH-DPAT (0.1 and 1 mg/kg) induced a marked and dose-related increase in the number of cells positive for Fos-LI in the locus coeruleus (LC), the main source of noradrenergic projections to the forebrain. This effect was also induced by the non-selective, partial 5-HT(1A) receptor agonist buspirone (10 mg/kg). The effect of both 8-OH-DPAT (0.1 mg/kg) and buspirone (10 mg/kg) on Fos-LI in the LC was blocked by pretreatment with the selective 5-HT(1A) receptor antagonist WAY 100635 (1 mg/kg). The active S(-)-enantiomer of the partial 5-HT(1A) receptor agonist (+/-)-MDL 75005EF (1 mg/kg) also induced the expression of Fos-LI in the LC, whereas the inactive R(+)-enantiomer of (+/-)-MDL 73005EF at the same dose did not. In addition to the LC, 8-OH-DPAT (0.1 mg/kg) also induced a marked increase in Fos-LI in various forebrain areas including the medial prefrontal cortex (infralimbic and cingulate cortical areas). More detailed analysis of the Fos response to 8-OH-DPAT in the medial prefrontal cortex revealed that the effect was attenuated by pretreatment with a combination of the beta(1)- and beta(2)-adrenoceptor antagonists ICI 118551 (4 mg/kg) and metoprolol (4 mg/kg), but not the alpha(1)-adrenoceptor antagonist prazosin (5 mg/kg). Taken together, the present findings provide immunocytochemical evidence that 5-HT(1A) receptor agonists activate noradrenergic neurones in the LC and that this leads to increased noradrenergic transmission at postsynaptic sites in the forebrain (specifically medial prefrontal cortex).

Tonic regulation of satiety by 5‐HT1B receptors in the mouse: converging evidence from behavioural and c‐fos immunoreactivity studies?

“…Conversely, antagonism of cell body autoreceptors by the 5‐HT 1A receptor antagonist WAY 100 635 indirectly decreases the firing rate of locus coeruleus neurons via stimulation of postsynaptic 5‐HT 2A receptors (Szabo & Blier, 2001). These findings are consistent with the reported enhancement of c‐ fos immunoreactivity within the locus coeruleus by the 5‐HT 1A receptor agonist 8‐OH‐DPAT (Hajos‐Korcsok & Sharp, 1999). Stimulation of 5‐HT 1B terminal autoreceptors would also be expected to decrease serotonergic inhibition of the locus coeruleus and lead to an increase in c‐ fos immunoreactivity in these cells.…”

Stereoselective and region-specific induction of immediate early gene expression in rat parietal cortex by blockade of neurokinin 1 receptors

“…Increased monoaminergic transmission is a candidate mechanism as Arc and c-fos expression in parietal cortex is activated by noradrenaline and 5-HT (eg. Hajós-Korcsok and Sharp, 1999;Pei et al, 2000). Thus, GR 205,171 causes a stereospecific increase both in the electrical activity of ascending noradrenergic neurones and in the release of cortical noradrenaline at a dose corresponding to that active in the present study (Millan et al, 2001).…”

Chronic Inactivation of the Orbitofrontal Cortex Increases Anxiety-Like Behavior and Impulsive Aggression, but Decreases Depression-Like Behavior in Rats

“…Although the contribution of 5-HT in the OFC to the emotional behavior such as anxiety- and depression-like behavior is less understood in rodents, it is reported that microinjection of 5-HT 1A or 5-HT 1B receptors agonist into the OFC suppressed aggressive behavior in mice (De Almeida et al, 2006; Centenaro et al, 2008; Stein et al, 2013). Also, systemic administration of 5-HT 1A receptor agonist or 5-HT reuptake inhibitor enhanced the firing of principal neurons and the expression of c-fos in the PFC (Hajós-Korcsok and Sharp, 1999; Jongsma et al, 2002; Lladó-Pelfort et al, 2012). Therefore, 5-HT may regulate affective behaviors via modulation of intrinsic neural activity in the OFC in addition to mediating the information from the OFC.…”