Functional Adaptation in the Brain Habenulo–Mesencephalic Pathway During Cannabinoid Withdrawal
Cells November 1, 2024 Sonia Aroni, Claudia Sagheddu, Marco Pistis et al. 6 citations
During cannabinoid withdrawal, the mesolimbic reward system shows reduced function, which may drive aversive states leading to relapse. The lateral habenula (LHb) exerts negative control over the ventral tegmental area (VTA) via the rostromedial tegmental nucleus (RMTg), suggesting a convergence point for opponent processes. In adult male rats treated with THC (15 mg/kg, i.p.) twice daily for 6.5–7 days, rimonabant-precipitated withdrawal reduced VTA dopamine neuron firing and burst activity, prolonged RMTg-evoked inhibition, and depressed spontaneous activity in both RMTg and LHb neurons. The authors propose that functional changes in the habenulo–mesencephalic circuit contribute to substance use disorders.