Striatal Mu Opioid Receptor Blockade Alters Methamphetamine‐Induced Stereotypy

Abstract

Methamphetamine (METH) induces stereotypy, which is characterized as inflexible, repetitive behavior. Enhanced activation of the patch compartment of striatum has been correlated with stereotypy, suggesting that stereotypy may be related to preferential activation of this region. Mu opioid receptors are densely expressed in the patch compartment and may contribute to stereotypy. The goal of this study was to determine if mu opioid receptor blockade alters METH‐induced stereotypy. Animals were bilaterally infused in the striatum with the mu antagonist CTAP (10 μg/μl) or vehicle. Animals were then given METH (7.5 mg/kg) or saline, placed in locomotor activity chambers and observed for 3h. Stereotypy was scored on a scale from 1‐10 in four behavioral dimensions: repetitiveness, frequency, duration and spatial distribution. Horizontal and rearing activity was also monitored during the 3h period. CTAP pretreatment significantly reduced the degree of stereotypy induced by METH. METH‐induced stereotypy is accompanied by spatial immobility and CTAP significantly reduced this effect. In support of this observation, CTAP pretreatment significantly increased horizontal locomotor activity in METH‐treated animals. There was also an increase in rearing activity in CTAP‐pretreated METH‐treated animals. These data indicate that striatal mu opioid receptor activation contributes to METH‐induced stereotypy.