The role of NOP receptors in psychomotor stimulation and locomotor sensitization induced by cocaine and amphetamine in mice

We have previously shown that orphanin FQ (also known as nociceptin; OFQ/N) attenuates the motor stimulatory effect of cocaine and blocks locomotor sensitization induced by cocaine. Furthermore, we have shown that cocaine treatment altered the level of endogenous OFQ/N, raising the possibility that endogenous OFQ/N and its receptor (NOP) may be crucial in these actions of cocaine. Accordingly, in the present study, we sought to determine the role of NOP receptors in psychomotor stimulation and locomotor sensitization induced by cocaine or amphetamine. Mice lacking the NOP receptor and their wild-type littermates were habituated to motor activity chambers for 1 h, injected with cocaine (0, 15 or 30 mg/kg) or amphetamine (0, 1 or 3 mg/kg), and motor activity was recorded for 1 h. For sensitization induced by these drugs, mice were treated with saline or the highest dose of each drug once daily for three consecutive days and tested on day 8. On this day, mice were habituated to the chambers for 1 h, then received a challenge dose of cocaine (15 mg/kg) or amphetamine (1 mg/kg), and motor activity was recorded for 1 h. Cocaine and amphetamine each induced hyperlocomotion but the extent of this response was not different between NOP receptor null mice and their controls. Sensitization developed to the motor stimulatory action of each drug, but the magnitude of cocaine-induced sensitization was only higher in null mice compared to their controls. Together, the present results suggest that the endogenous OFQ/N/NOP receptor system may modulate the development of cocaine-induced locomotor sensitization.