Role of hippocampal alpha(2A)-adrenergic receptor in methamphetamine-induced hyperlocomotion in the mouse

Psychostimulants, such as methamphetamine (METH), induce psychological dependence and we recently suggested that hippocampal alpha(2A)-adrenergic receptor (alpha(2A)-AR) is involved in METH-induced modulation of central nervous systems. The present study shows that pretreatment with yohimbine dose-dependently decreased the ambulatory hyperactivities induced by METH (2 mg/kg) in mice. Moreover, specific knock-down of the hippocampal alpha(2A)-AR with infusion of anti-sense oligo DNA of alpha(2A)-AR significantly suppressed ambulatory activity induced by METH administration. Infusion of sense oligo DNA of alpha(2A)-AR into mouse hippocampus exerted no effects on the ambulatory activity. These observations strongly suggest the involvement of hippocampal alpha(2A)-AR in the regulation of ambulatory activity induced by METH administration.