Exercise against cocaine sensitization in mice: a [¹⁸F]fallypride micro-PET study.

Area of Science:

• Neuroscience
• Exercise Physiology
• Pharmacology

Background:

• Aerobic exercise, like wheel running in rodents, shows promise in mitigating drug addiction vulnerability.
• The precise neurobiological mechanisms behind exercise's protective effects against addictive substances remain largely unknown.
• Understanding these mechanisms is crucial for developing novel therapeutic strategies for substance use disorders.

Purpose of the Study:

• To investigate the neurobiological underpinnings of wheel-running exercise's protective effects against cocaine-induced behavioral responses in mice.
• To assess the impact of chronic wheel running on locomotor activity, cocaine sensitization, and dopamine D2/3 receptor availability.

Main Methods:

• Female C57BL/6J mice were divided into exercised (running wheel) and control groups for 6 weeks.
• Locomotor activity was measured following acute cocaine administration and during sensitization protocols.
• Positron emission tomography (PET) with [18F]fallypride was used to quantify dopamine D2/3 receptor binding potential in the striatum.

Main Results:

• Exercised mice exhibited reduced sensitivity to acute cocaine effects and attenuated locomotor sensitization.
• This protective effect was particularly pronounced in the long-term expression of cocaine sensitization.
• Wheel running was associated with a moderate decrease in striatal dopamine D2/3 receptor density, while chronic cocaine increased receptor binding potential.

Conclusions:

• Wheel-running exercise confers protection against the acute and sensitized locomotor effects of cocaine in mice.
• A potential mechanism involves exercise-induced alterations in dopamine D2/3 receptor availability in the striatum.
• These findings highlight exercise as a potential non-pharmacological intervention for reducing vulnerability to drug addiction.