CIRCULATING ADRENAL HORMONES ARE NOT NECESSARY FOR THE DEVELOPMENT OFSENSITIZATION TO THE PSYCHOMOTOR ACTIVATING EFFECTS OF AMPHETAMINE

We reported previously that when amphetamine is given in NOVEL test ca ges both its acute psychomotor activating effects (rotational behavior and locomotor activity) and the degree of sensitization are greater t han when amphetamine is given in HOME cages that are physically identi cal to the NOVEL test cages. Since exposure to the NOVEL environment i ncreases plasma corticosterone levels (Experiment 1) it is possible th at the enhancement in the effects of amphetamine in the NOVEL conditio n is mediated by corticosterone. If this hypothesis is correct adrenal ectomy (ADX) should abolish the difference between the HOME and NOVEL groups. This was tested in three independent experiments, in which the response (rotational behavior in Experiments 2 and 3; locomotor activ ity and rearing behavior in Experiment 4) to repeated injections of am phetamine was assessed in rats that underwent adrenalectomy (ADX) or a sham operation (SHAM). ADX animals received either no corticosterone replacement or one of two corticosterone replacement treatments. Adren alectomy, with or without corticosterone replacement treatment, had no significant effect on the development of amphetamine sensitization, e ither in the HOME or the NOVEL environment. By contrast, the effects o f adrenalectomy on the acute response to amphetamine varied depending on the behavioral measure and possibly on the dose of amphetamine (2.0 mg/kg, 3.0 mg/kg and 1.5 mg/kg IP, in Experiments 2, 3 and 4, respect ively). We conclude that: (i) a stress-induced secretion of adrenal ho rmones is not responsible for the enhancement in sensitization to amph etamine seen in animals tested in a NOVEL environment; (ii) circulatin g adrenal hormones are not necessary for development of sensitization to the psychomotor activating effects of amphetamine.