D-Serine and D-Cycloserine Reduce Compulsive Alcohol Intake in Rats.

摘要: There is considerable interest in NMDAR modulators to enhance memory and treat neuropsychiatric disorders such as addiction, depression, schizophrenia. D-serine D-cycloserine, the activators at glycine site, are of particular because they have been used humans without serious adverse effects. Interestingly, also inhibits some NMDARs active hyperpolarized potentials (HA-NMDARs), we previously found that HA-NMDARs within nucleus accumbens core (NAcore) critical for promoting compulsion-like alcohol drinking, where rats consume despite pairing with an aversive stimulus quinine, a paradigm considered model compulsive aspects human use (AUDs). Here, examined impact D-cycloserine on this aversion-resistant intake (that persists adulteration quinine) consumption quinine-free alcohol. Systemic reduced altering or saccharin quinine. Importantly, NAcore but not dorsolateral striatum selectively drinking. In addition, inhibited EPSCs evoked −70 mV vitro by optogenetic stimulation mPFC–NAcore terminals alcohol-drinking rats, similar reported effects blocker AP5. Further, preexposure occluded AP5 inhibition mPFC-evoked EPSCs, suggesting inhibiting HA-NMDARs. quinine-adulterated alcohol, vitro. Our results indicate HA-NMDAR can reduce support testing immediately accessible, FDA-approved drugs AUDs.