Systemic and intra-accumbens microinjections of naltrexone interfere with tolerance to ethanol in rats

Abstract

The results suggest that the opioid system may be involved in the development of ethanol tolerance, and that the nucleus accumbens may play a role in this phenomenon.

Selective mu- and kappa-opioid receptor antagonists administered into the nucleus accumbens interfere with rapid tolerance to ethanol in rats

“…1). Repeated injection of ethanol led to rapid tolerance on day2 in control groups, in accordance with previous studies Morato 2002, 2003;Varaschin et al 2005). Pretreatment with the mu-opioid antagonist naloxonazine directly into the core or shell portions of the nucleus accumbens prevented the onset of tolerance to ethanol (Fig.…”

“…Thus, one alternative interpretation is that nor-binaltorphimine may have facilitated one-trial tolerance in the tilting plane apparatus. This phenomenon has been described previously for animals tested for anxiety in the elevated plus maze (File et al 1990;Dawson et al 1994;Bertoglio and Carobrez 2002) Interestingly, we observed the same pattern of behavior after systemic injection of a high dose (3 mg/kg) of naltrexone (Varaschin et al 2005). Additionally, norbinaltorphimine is a long-acting antagonist (Butelman et al 1993) and, although we did not observe changes in baseline on day2 (data not shown), the possibility that this drug had a residual effect on day2 cannot be discarded.…”

“…In our previous work, unilateral injection of naltrexone into either core or shell portions of the nucleus accumbens prevented the onset of rapid tolerance to ethanol (Varaschin et al 2005). Numerous studies have demonstrated biochemical and behavioral effects followed by unilateral intra-accumbens injections of pharmacological agents.…”

“…2), an effect similar to that observed with i.p. and intra-accumbens naltrexone injection (Varaschin et al 2005).…”

“…More recently, we reported that naltrexone, whether injected systemically or directly into the nucleus accumbens, prevented the onset of tolerance to ethanol in a model of rapid tolerance to motor incoordination (Varaschin et al 2005). However, due to the limited selectivity of this antagonist, it was not possible to identify which opioid receptor subtypes are involved in this behavior.…”