INDUCTION BUT NOT EXPRESSION OF BEHAVIORAL SENSITIZATION TO NICOTINE IN THE RAT IS DEPENDENT ON GLUCOCORTICOIDS

Behavioural sensitization has been implicated in the development of ad dictive behaviour, and several studies suggest that corticosteroids ma y be involved in this phenomenon. In the present study, the effects of adrenalectomy and steroid replacement treatments on the behavioural s ensitization observed after daily injections of nicotine (0.4 mg/kg s. c.) were investigated in the rat. Adrenalectomy completely prevented s ensitization to the locomotor stimulating effect of nicotine after rep eated injections but did not influence the acute locomotor activating effect of the drug or an already established sensitization to nicotine . In adrenalectomized animals receiving replacement treatment with cor ticosterone or dexamethasone, but not aldosterone, repeated administra tion of nicotine produced behavioural sensitization. Repeated dexameth asone treatment per se failed, however, to sensitize rats to nicotine. Post mortem neurochemical studies showed that repeated administration of nicotine significantly increased homovanillic acid (HVA) levels, a s well as the dihydroxyphenylacetic acid (DOPAC)/dopamine quotient, in the limbic forebrain. Adrenalectomy per se significantly increased HV A levels and tended to elevate the DOPAC/dopamine quotient. When repea tedly treated with nicotine, adrenalectomized rats displayed a higher DOPAC/dopamine quotient, but no significant difference in HVA levels, compared to nicotine-treated sham-operated controls. In the striatum a nd the cortex, no significant effects of nicotine treatment or adrenal ectomy were observed on any of the neurochemical measures. The present results suggest that glucocorticoid (type II) receptor activation is required for induction of sensitization to the locomotor stimulatory e ffect of nicotine, whereas corticosteroids are not required for the ex pression of the behavioural sensitization once established. Provided t hat HVA levels and the DOPAC/dopamine quotient relatively well reflect the presynaptic dopamine activating effect of nicotine, it may be sug gested that corticosteroid-related mechanisms associated with behaviou ral sensitization to nicotine are post- rather than presynaptically lo cated in relation to mesolimbic dopamine neurons.