Role of prefrontal dopaminergic neurotransmission in glucocorticoid receptor-mediated modulation of methamphetamine-induced hyperactivity.

Glucocorticoids are involved in psychostimulant-induced hyperactivity, but the exact mechanism is not known. This study used the selective glucocorticoid receptor antagonist, RU-43044, to determine whether prefrontal neurotransmission is involved in glucocorticoid-mediated modulation of methamphetamine (METH)-induced hyperactivity in mice. Pretreatment with RU-43044 (10-30 mg/kg) attenuated the increased spontaneous locomotor activity induced by METH (1-2 mg/kg). The psychostimulant effect of METH was also attenuated by adrenalectomy. RU-43044 inhibited METH-induced increases in extracellular dopamine (DA), but not serotonin (5-HT), levels in the prefrontal cortex, but did not affect METH-induced increases in extracellular DA levels in the nucleus accumbens shell, although it inhibited increases in extracellular 5-HT levels. Adrenalectomy also attenuated the METH-induced increases in extracellular DA levels in the prefrontal cortex. RU-43044 did not affect METH-induced increases in plasma corticosterone levels. These findings suggest that glucocorticoid receptors are involved in METH-induced hyperactivity, and that prefrontal dopaminergic neurotransmission plays a role in glucocorticoid-mediated modulation of METH-induced behavioral changes.