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

✍ Scribed by Éva Hajós-Korcsok; Trevor Sharp

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 485 KB
• Volume: 34
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/(sici)1098-2396(199911)34:2<145::aid-syn7>3.0.co;2-d

✦ Synopsis

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 (Ϯ)-MDL 75005EF (1 mg/kg) also induced the expression of Fos-LI in the LC, whereas the inactive R(ϩ)-enantiomer of (Ϯ)-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 ␤ 1 -and ␤ 2 -adrenoceptor antagonists ICI 118551 (4 mg/kg) and metoprolol (4 mg/kg), but not the ␣ 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).