The frequency of cocaine administration impacts cocaine-induced receptor alterations.

The present study investigated the impact of dosing schedule on cocaine-induced receptor alterations. Rats were injected with 30 mg/kg per day of cocaine given either as a single injection or in two equally divided doses for 14 days. The effects of these two dosing regimens were compared with our previous findings following administration of cocaine three times daily at 1-h intervals. Using receptor autoradiography, twice daily injections of cocaine produced an upregulation of mu opioid receptors in the rostral nucleus accumbens, rostral caudate putamen, and layer I of the rostral cingulate cortex, whereas single daily injections resulted in a significant increase in the nucleus accumbens only. Only small insignificant increases in kappa opioid receptor densities were found following either once or twice daily cocaine injections, whereas three daily injections produced an increase in kappa receptor density in the cingulate cortex, nucleus accumbens, and caudate putamen. Increased dopamine D1 receptor binding was found in the nucleus accumbens and olfactory tubercle following twice daily cocaine injections, but not after single daily injections of the same total daily dose. These results demonstrate that the same total daily dose of cocaine administered in multiple small injections produces a greater effect on receptor regulation than a single larger injection. This suggests that the interval between cocaine injections is an important variable when studying the effects of cocaine on neurochemistry.