Locomotion, stereotypy, and dopamine D 1 receptors after chronic “binge” cocaine in C57BL/6J and 129/J mice

Abstract

We have shown that C57BL/6J and 129/J mice differ in their behavioral response to “binge” pattern cocaine (three daily injections of 15 mg/kg separated by 1 h). To determine if these differences persist during chronic binge cocaine administration, we examined the effects of 14-day binge pattern cocaine on home cage behavior. Since the dopamine D 1 receptor may be an important mediator of cocaine-induced locomotor activity, we examined binding to the dopamine D 1 receptor. Locomotor activity was increased by chronic binge cocaine in C57BL/6J ( P<.0001) but not in 129/J mice. C57BL/6J mice developed tolerance to the locomotor-activating effects of cocaine. Stereotypic responses were greater in C57BL/6J than in 129/J mice ( P=.03), with neither tolerance nor sensitization in either strain. Dopamine D 1 receptor binding in the nucleus accumbens and olfactory tubercle did not differ between strains and was not affected by chronic binge cocaine. In the caudate putamen, subregion specific strain differences in dopamine D 1 receptor binding were observed; chronic binge cocaine increased dopamine D 1 receptor binding in the caudal ( P<.05), but not rostral caudate putamen. There was no correlation between locomotor activity or stereotypy and dopamine D 1 receptor density. Thus, with chronic binge cocaine administration, behavioral differences persist between the C57BL/6J and 129/J mice, and cocaine-induced locomotor activity is not correlated with changes in dopamine D 1 receptor binding.