L-Cysteine reduces oral ethanol self-administration and reinstatement of ethanol-drinking behavior in rats

Our previous findings have shown that L-cysteine, a non essential amino acid, prevented ethanol (EtOH)
induced conditioned place preference. The aim of the present study was to examine the effect of L-cysteine
on the acquisition and maintenance of oral EtOH self-administration and on the reinstatement of EtOHdrinking
behavior in Wistar rats. Rats were pretreated intraperitoneally with saline or L-cysteine (20 and
40 mg/kg) 30 min before each acquisition trial, in an operant nose-poking paradigm where they were given
the opportunity to orally self-administer tap water or EtOH (5–10% v/v). Further, to evaluate if L-cysteine
reduces the acquired oral EtOH self-administration, we carried out an independent experiment in which rats
were trained to self-administer EtOH (10%); after all groups of rats developed similarly stable oral EtOH selfadministration,
the effect of L-cysteine (0, 40, 60, 80 and 100 mg/kg) was tested. An additional group of rats
was pretreated with saline or L-cysteine (80 mg/kg) and tested on reinstatement after EtOH extinction and,
at the end of last reinstatement session, were utilized to measure blood and brain EtOH levels. The animals
that had access to EtOH solution discriminated between the active and inactive nose-pokes and showed rates
of active nose-pokes significantly higher than the tap water group. Furthermore, rats self-administering
EtOH (10%) also demonstrated extinction behavior and gradually reinstated active nose-poke responding
when EtOH was reintroduced. L-cysteine reduced both the acquisition and maintenance of oral EtOH selfadministration.
The reduced reinstatement of EtOH-drinking behavior was paralleled by a significant
reduction of EtOH intake and correlated with blood and brain EtOH levels. The efficacy of L-cysteine on the
various phases of alcohol drinking in rats, could represent an interesting pharmacological approach and
could open a new line of research for the development of therapies to reduce EtOH intake in alcoholic
patients.