Effects of morphine on intracranial self-stimulation : the involvement of associative factors and the role of ventral tegmental dopamine neurons

A series of experiments was carried out to clarify the effects of morphine (0.3 - 10 mg/kg) on intracranial self-stimulation (ICS) and to compare these with the effects of the stimulant amphetamine on this behavior. It was shown that the enhancement of ICS by morphine requires repeated drug exposure, is prevented by pre-exposure to the drug in a non-ICS context, is mimicked by administration of vehicle, and is not reliably reversed by naloxone. In contrast, facilitation of ICS by amphetamine was immediate and remained stable over repeated days of testing. It was concluded that ICS facilitation induced by morphine, but not by amphetamine, is largely the outcome of a learned association between the drug effect and the ICS procedure, and does not appear to be a direct, opiate receptor-mediated effect. Finally, 6-OHDA lesions of ventral tegmental dopamine neurons were shown to block the facilitation of ICS by morphine but not by amphetamine. These lesions were also shown to delay the development of tolerance to morphine-induced catalepsy