5-Hydroxytryptamine and corticosterone in an animal model of depression.
1. Rat plasma corticosterone increases during 2 hr restraint stress. The animals then exhibit hypophagia and decreased locomotion occurs on placement 24 hr later in an open field. Repeating the restraint daily for 5-7 days leads to adaptation. Failure to adapt is the depression model which is associated with three factors implicated in the illness ie increased plasma glucocorticoid level, female sex and inadequate 5-HT function as revealed by behavioural response to the agonist 5-methoxy-N,N-dimethyl 5-HT. However, the greater stress induced rise of corticosterone in female rats may reflect a greater response to activation of hypothalamic 5-HT receptors mediating corticoid release. 2. The model responds appropriately to chronic antidepressant pretreatment. Single injections of 5-HT1A agonists (8-OH-DPAT, buspirone, ipsapirone, gepirone) but not of benzodiazepine anxiolytics have similar effects. Therefore, 5-HT1A agonists may have antidepressant activity. Both behavioural and neurochemical evidence indicates that the adaptive effects of 5-HT1A agonists on the depression model are associated with desensitisation of somatodendritic 5-HT1A autoreceptors.
Curzon
G
G
Institute of Neurology, London, England.
D000818:Animals; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000097:blood* / Q000188:drug therapy; D004195:Disease Models, Animal; D051381:Rats; D012149:Restraint, Physical; D012701:Serotonin / Q000097:blood*; D012702:Serotonin Antagonists / Q000627:therapeutic use
D012702:Serotonin Antagonists; D012701:Serotonin; D003345:Corticosterone