Alteration in 5-hydroxytryptamine agonist-induced behaviour following a corticosterone implant in adult rats.
Hypercortisolism and altered serotonergic function may account for the pathological symptoms seen in depression. This study examines the impact of 4 days continuous corticosterone treatment on 5-HT agonist-induced behaviour to delineate changes in 5-HT receptor function in the adult rat. The flat body posture, reciprocal forepaw treading, elevated corticosterone, hyperglycaemia, hypothermia and reduced hippocampal 5-HT induced by the 5-HT(1A) agonist 8-OHDPAT (0.3 mg/kg ip) were all significantly attenuated by the corticosterone implant. The elevation in plasma corticosterone and back muscle contractions evoked by the 5-HT(2A) agonist DOI (1 mg/kg ip) were attenuated, whilst wet-dog shakes were enhanced by corticosterone treatment. 5-HT(2B) agonist-induced behaviour and the hypolocomotion and hypophagia induced by the 5-HT(2C) agonist m-CPP (2.5 mg/kg ip) were unaltered but the mCPP-induced elevation in corticosterone was abolished by corticosterone treatment. Hypothalamic 5-HT receptors mediating corticosterone- and 5-HT(1A) receptors, whether on serotonergic nerve terminals or postsynaptic neurones, were downregulated by corticosterone treatment. In contrast, 5-HT(2A) receptors may be up- or downregulated dependent on whether they are on supraspinal or spinal neurones, respectively. A comparison of the brain region-dependent alteration in serotonergic function produced by hypercorticosterone in the rat with that seen in depression is discussed.
Fone
Kevin C F
KC
School of Biomedical Sciences, Queen's Medical Centre, University of Nottingham, NG7 2UH, Nottingham, UK. kevin.fone@nottingham.ac.uk
Topham
Ian A
IA
D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001831:Body Temperature / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D004343:Drug Implants; D004435:Eating / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology
C092430:1-(5-(2-thenyloxy)-1H-indol-3-yl)propan-2-amine; D000662:Amphetamines; D001786:Blood Glucose; D004343:Drug Implants; D007211:Indoles; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D013876:Thiophenes; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine; D003345:Corticosterone