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Effect of 5‐HT 1A receptor ligands on Fos‐like immunoreactivity in rat brain: Evidence for activation of noradrenergic transmission
Author(s) -
HajósKorcsok Éva,
Sharp Trevor
Publication year - 1999
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199911)34:2<145::aid-syn7>3.0.co;2-d
Subject(s) - 5 ht1a receptor , agonist , chemistry , locus coeruleus , endocrinology , medicine , forebrain , partial agonist , infralimbic cortex , buspirone , 8 oh dpat , serotonin agonist , prefrontal cortex , receptor , 5 ht receptor , serotonin , pharmacology , neuroscience , central nervous system , biology , biochemistry , cognition
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 β 1 ‐ and β 2 ‐adrenoceptor antagonists ICI 118551 (4 mg/kg) and metoprolol (4 mg/kg), but not the α 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). Synapse 34:145–153, 1999. © 1999 Wiley‐Liss, Inc.