Possible Interaction: Acetylcysteine and Cocaine

“Time-course studies revealed that cocaine treatment persistently downregulated miR-124 in NAc.”

“Cocaine maintained responding during placebo and n-acetylcysteine maintenance, but the reinforcing effects of cocaine were significantly attenuated across both maintenance conditions in participants maintained on n-acetylcysteine first compared to participants maintained on placebo first.”

“Specific synaptic and cellular changes in the NAc persist following prolonged exposure to cocaine , and this remodeling may contribute to altered behavior.”

“ NAC also decreased desire for cocaine in a cue-reactivity procedure as measured by psychophysical and subjective data in response to slides depicting cocaine and cocaine use (LaRowe et al, 2007).”

“Collectively, these data demonstrate that N-acetyl cysteine diminishes the motivational qualities of a cocaine challenge injection possibly by altering pathogenic drug-induced plasticity.”

“Interestingly, repeated administration (7 days) of N-acetyl cysteine (60 mg/kg, IP) produced a significant reduction in cocaine (10 mg/kg, IP)-induced reinstatement, even though rats (N=10–12/group) were tested 24 h after the last administration of N-acetyl cysteine.”

“ObjectivesThe present studies examined the impact of chronic cocaine exposure on touchscreen-based models of learning (repeated acquisition) and cognitive flexibility (discrimination reversal) and, also, the ability of NAC to modulate cocaine self-administration and its capacity to reinstate drug-seeking behavior.”

“SIGNIFICANCE STATEMENT These studies identified a sequence of neural events whereby reexposure to cocaine activates a signaling cascade that alters synaptic strength in the NAc shell and triggers a behavioral response driven by a drug-associated memory.”

“Using a mouse behavioral sensitization model, we demonstrated that acute cocaine (AC; 0.5h) treatment significantly decreased Dnmt1, Dnmt3a, Tet1, and Tet2 mRNA levels in the NAc and PBC, whereas at 24h after AC treatment, Dnmt mRNA expression and enzyme activity levels were significantly increased.”

“Withdrawal from repeated cocaine also enhances AMPAR signaling in NAc core MSNs.”

“Conclusions Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.”