Abstract :
[en] Preclinical studies suggest that free access to a running wheel can attenuate the behavioural responsiveness to addictive drugs in rodents. Regarding the behavioural responsiveness to drugs, psychomotor sensitization has an integral role in the process of drug addiction in craving and relapse (Steketee and Kalivas, 2011). Free wheel-running was recently shown to be efficacious at preventing the initiation or the long-term expression of psychomotor sensitization to cocaine in mice or rats (Diaz et al., 2013; Geuzaine and Tirelli, 2014). In the present study, we investigated the neuro-functional correlates of the protection against psychomotor sensitization to cocaine afforded by free wheel-running on dopaminergic neurotransmission, using microPET imaging with [18F]Fallypride, a Dopamine 2 receptor (D2R) antagonist.
We used a total of 32 female C57BL/6J mice. At 28 days of age, the mice were randomly assigned to on of the two experimental housing conditions, defined by the presence or the absence of a running wheel in the cage (pre-testing period: 6 weeks). Since mice from the two types of housing received either saline or cocaine (8 mg/kg, i.p.) during testing (9 days), a basic 2*2 factorial design was generated (two-way ANOVA). The whole experimentation lasted 85 days, included the 42-days pre-testing period and the 3 weeks (housing condition, no injection) between the testing and the long-term expression of sensitization (LTES). All mice underwent a microPET (Focus 120, Siemens) the day after the LTES. The microPET protocol consisted of a 60 min. dynamic acquisition after the injection of 10 MBq of [18F]Fallypride in the tail vein.
We observe a strong attenuating effect of exercise on the expression of sensitization to cocaine (Effect Size = 2.66 at p < .001 one-tailed, N.B: Effect Size is the mean difference in standard deviation units). Regarding the microPET outcomes ([18F]Fallypride Binding Potential, BP), we have a significant increase of the [18F]Fallypride BP for the cocaine-treated mice, compared to the saline-injected mice (Effect Size = 0.78 at p = .02 one-tailed). We observe a decrease tendency of the [18F]Fallypride BP in the exercise condition compared to the sedentary condition (ES = 0.48 at p = .09 one-tailed).
These findings indicate that LTES is associated with an increase of the [18F]Fallypride BP in the mouse striatum, probably reflecting an increase in postsynaptic D2R density in this region. Besides that, the protecting effect of free running on psychomotor sensitization goes together with a decrease in D2R density in the striatum of exercised mice. Those data will be augmented with identical sub-experiment. All data will be pooled together to reach a total number of 64 mice (n = 16 per group).
