grantor:
University of TorontoThe aim of this thesis was to investigate the role of the neuropeptide substance P (SP) in mediating relapse to drug-seeking behaviour in rats. Experiment 1 showed that the SP analogue, DiMe-C7 (0, 1, 3, or 6[mu]g/[mu]l; 0.51/side) microinjected into the ventral tegmental area (VTA) significantly increased locomotor activity at all drug doses tested. Experiment 2 showed that intra-VTA injections of DiMe-C7 (0, 0.2, 1 or 5[mu]g/[mu]l) induced reinstatement of drug-seeking behaviour in a dose-dependent manner in animals previously trained to self-administer cocaine. Finally, experiment 3 showed that pre-treatment with the selective NK-1 receptor antagonist, Spantide II (0 or 1 [mu]g/0.5[mu]l), by injection into the VTA, did not block DiMe-C7 (0 or 1 [mu]g/0.5[mu]l)-induced reinstatement of cocaine-seeking behaviour, suggesting that DiMe-C7-induced reinstatement may not be dependent upon NK-1 receptor activation in the VTA. Together, these findings provide evidence for the role of SP and neurokinin receptors in drug relapse.M.A
