Reduced-5-hydroxytryptamine-dependent behavior in rats following chronic corticosterone treatment

The effect of chronic corticosterone treatment (50 mg/kg s.c. 2 x daily) for up to 4 days on behavioural responses to drugs affecting 5-hydroxytryptamine (5-HT) and dopamine (DA) systems was examined in rats 20 h after the last treatment, when placed in experimental cages, to which they had become habituated. Corticosterone- and vehicle-treated rats exhibited both comparable spontaneous behavior when given 0.9% NaCl i.p. and showed similar behavioural responses following amphetamine (3 mg/kg i.p.). However, responses to the 5-HT-releasing drug p-chloroamphetamine (PCA, 4 mg/kg i.p.) were altered with decreased head-weaving hind-limb abduction and forepaw treading. Postsynaptic changes appear to be involved as responses to the 5-HT agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 5 mg/kg i.p.) (tremor, hind-limb abduction and forepaw treading) were also decreased. Hind brain and striatal concentration of 5-HT, DA and their metabolites were comparable in corticosterone and vehicle treated rats killed 20 h after the last treatment. Brain PCA levels determined 30 min after injection were also comparable in both groups. PCA induced behaviour was not altered 20 h after 1 day corticosterone treatment or 4 day after 1 day treatment and 5-MeODMT-induced behaviour was not altered 20 h after 14 days treatment with a lower dose of corticosterone (10 mg/kg s.c. x 2). Twenty h after 1 day corticosterone treatment (50 mg/kg s.c. x 2), rats placed in an open field for the first time showed significantly more activity and dropped fewer faecal pellets than controls.(ABSTRACT TRUNCATED AT 250 WORDS)