Effects of central neurokinin-1 receptor antagonism on cocaine- and opiate-induced locomotor activity and self-administration behaviour in rats.

The neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 (NK-1) receptor, have been implicated in some of the reward-related behavioural effects of abused drugs, including psychostimulants and opiates. The first objective of the present series of experiments was to assess the role of the NK-1 receptor in two reward-related behavioural effects of cocaine: locomotor activity and self-administration. In tests for locomotor activity, rats were given intracerebroventricular (ICV) infusions of the selective NK-1 receptor antagonist, GR82334 (0, 10, 50 pmol), prior to systemic injections of cocaine. In self-administration experiments, rats were trained to self-administer cocaine on a fixed-ratio 5 (FR5) schedule of reinforcement. Following acquisition of stable responding, animals were pretreated with GR82334 (0, 2, 10, 50 pmol; ICV) prior to subsequent self-administration sessions. Based on evidence suggesting a potentially selective role for NK-1 receptors in opiate reward, we also examined the effects of GR82334 on morphine-induced locomotor activity and heroin self-administration. Results showed that GR82334 had no effect on cocaine-induced locomotor activity or cocaine self-administration, but attenuated morphine-induced locomotor activity and increased heroin self-administration. These findings suggest that endogenous activity at NK-1 receptors may play a specific role in opiate-induced, but not cocaine-induced, locomotor activation and reinforcement.