The ClockΔ19 mutation in mice fails to alter the primary and secondary reinforcing properties of nicotine

Abstract

Background: Clock genes have been demonstrated to play a role in behavioral responses to a variety of drugs of abuse, including cocaine, amphetamine, morphine, and ethanol. However, no studies to date have examined the role of Clock genes on nicotine-mediated behaviors. We examined the involvement of Clock, one of several Clock genes, on the effects of nicotine by examining mice with the ClockΔ19 mutation in behaviors commonly used to assess drug effects in rodents.

Methods: We first measured the locomotor effects of nicotine in mutants and wild type mice in response to repeated nicotine injections (0.175 mg/kg, IP). To assess the secondary properties of nicotine, we measured the ability of nicotine (0.175 mg/kg, IP) to induce a conditioned place preference. Finally, we measured the primary reinforcing properties of nicotine at two doses (0.01 and 0.03 mg/kg/infusion, IV) using the self-administration paradigm.

Results: Mutant mice demonstrated no difference in magnitude of the sensitized response to nicotine as compared to wild-type controls. In the conditioned place preference paradigm, mutant and wild-type mice demonstrated a similar preference for a nicotine-paired environment. And finally, mutant and wild-type mice demonstrated a similar acquisition of nicotine self-administration, as indicated by the number of responses on a nicotine-paired lever and the number of nicotine reinforcers achieved during sessions.

Conclusions: The ClockΔ19 mutation appears to have no effect on the reinforcing properties of nicotine, in contrast to its demonstrated role in cocaine reinforcement. Further studies are needed to determine the effect of other Clock genes on nicotine reinforcement.

Keywords: Clock; ClockΔ19 mutant mice; Conditioned place preference; Locomotor sensitization; Nicotine; Self-administration.