The role of substance P and brain neurokinin-1 receptors in relapse to drug-seeking behaviour, drug-induced locomotor activity and drug self-administration
Subtitle: y Franca M. Placenza.
Published: 2006
Language: eng
Number of pages: 175
ISBN-13: 9780494159347
Description: These latter findings prompted the third series of experiments which investigated the role of NK-1 receptors in other reward-related behavioural effects of cocaine, and whether, as suggested by previous studies, NK-1 receptors may play a differential role in cocaine- and opiate-induced behaviours. Results showed that ICV administration of GR82334 attenuated morphine-, but not cocaine-induced locomotor activation, and increased heroin, but not cocaine self-administration. In contrast, [Sar9Met(O2)11]-SP decreased both cocaine and heroin self-administration. These findings suggest that while activation of NK-1 receptors may be capable of altering the reinforcing effects of both cocaine and heroin, endogenous activity at NK-1 receptors plays a specific role in opiate-induced locomotor activation and reinforcement.The primary objective of this dissertation was to investigate the role of the neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 (NK-1) receptor, in the reinstatement of cocaine-seeking behaviour. This investigation was prompted by findings demonstrating extensive interactions between SP and the midbrain dopamine (DA) system, and those suggesting that these interactions may play a role in some drug-induced behaviours.The first series of experiments extended an initial finding that injection of the SP analogue, DiMe-C7, into the ventral tegmental area (VTA) induces reinstatement of cocaine-seeking behaviour by showing that a DA D1-, but not D2-like, receptor antagonist attenuated DiMe-C7-induced reinstatement, and that intra-VTA DiMe-C7 selectively increased c-fos mRNA expression in the medial prefrontal cortex (PFC) and nucleus accumbens (NAcc). These findings suggest that the midbrain DA system, specifically D1-like receptor mechanisms, are involved in DiMe-C7-induced reinstatement, and that the medial PFC and NAcc may represent possible neuroanatomical sites mediating this effect.A second series of experiments examined the specific role of NK-1 receptors in reinstatement of cocaine-seeking behaviour, and cocaine-primed reinstatement. Results showed that ICV administration of the selective NK-1 receptor agonist, [Sar9Met(O2)11]-SP, induced reinstatement of cocaine-seeking behaviour, but that the selective NK-1 receptor antagonists, GR82334 and RP67580, had no effect on cocaine-induced reinstatement. These findings suggest that although activation of NK-1 receptors is capable of inducing reinstatement of cocaine-seeking behaviour, endogenous activity at NK-1 receptors does not play a role in cocaine-primed reinstatement.
Notes: Source: Dissertation Abstracts International, Volume: 67-07, Section: B, page: 4150.

Thesis (Ph.D.)--University of Toronto, 2006.

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