Induction of Fos proteins in regions of the nucleus accumbens and ventrolateral striatum correlates with catalepsy and stereotypic behaviours induced by morphine

Abstract

A history of intermittent exposures to drugs of abuse can cause long-term changes in acute behavioural responses to a subsequent drug exposure. In drug-naive rats, morphine can elicit intermittent cataleptic postures followed by sustained increases in locomotor activity. Chronic intermittent morphine treatment can reduce catalepsy and increase locomotor behaviour and stereotypy induced by morphine, even after prolonged periods of abstinence. The nucleus accumbens and limbic basal ganglia circuitry are implicated in the expression of various morphine-induced motor behaviours and catalepsy. We examined the effect of intermittent morphine exposure on the distribution of Fos proteins in the basal ganglia following a subsequent morphine challenge administered after a period of drug abstinence. We found that such exposures increased c-Fos induced by a morphine challenge in accumbens core regions that were immunoreactive for the μ-opioid receptor, and this correlated with the frequency of stereotypic behaviours displayed by the rats. We also found that a history of morphine exposures increased c-Fos in the ventrolateral striatum in response to a morphine challenge following 14 d but not 24 h of drug abstinence. In contrast, such a history induced acute Fras in the nucleus accumbens in response to a morphine challenge following 24 h but not 14 d of morphine abstinence. These data provide further confirmation that psychomotor sensitisation induced by repetitive morphine exposure involves long-term neuroadaptations in basal ganglia circuitry particularly at the level of the nucleus accumbens.