Neuro-functional correlates of protective effects of wheel-running exercise against cocaine locomotor sensitization in mice: a [18F]fallypride microPET study

Abstract

ABSTRACTWheel-running exercise in laboratory rodents (animal model useful to study the neurobiology of aerobic exercise) decreases behavioral markers of vulnerability to addictive properties of various drugs of abuse including cocaine. However, neurobiological mechanisms underpinning this protective effect are far from being fully characterized and understood. Here, 28-day-old female C57BL/6J mice were housed with (n=48) or without (n=48) a running wheel for 6 weeks before being tested for acute locomotor responsiveness and initiation of locomotor sensitization to intraperitoneal injections of 8 mg/kg cocaine. The long-term expression of sensitization took place 3 weeks after the last session. On the day after, all mice underwent a microPET imaging session with [18F]fallypride radiotracer (dopamine 2/3 receptor (D2/3R) antagonist). Exercised mice were less sensitive to acute and sensitized cocaine hyperlocomotor effects, such attenuation being particularly well-marked for long-term expression of sensitization (η2p = 0.262). Additionally, we found that chronic administrations of cocaine was associated with a clear-cut increase of [18F]fallypride binding potential in mouse striatum (η2p = 0.170), presumably reflecting an increase in postsynaptic D2/3R density in this region. Finally, we found evidence that wheel-running exercise was associated with a moderate decrease in D2/3R density in striatum (η2p = 0.075), a mechanism that might contribute to protective properties of such form of exercise against drugs of abuse vulnerability.