Disruption of Long-Term Alcohol-Related Memory Reconsolidation: Role of β-Adrenoceptors and NMDA Receptors

Anton N M Schoffelmeer,Leontien Diergaarde,Yvar Van Mourik,Danai Riga,Jelte A Wouda,Taco J De Vries

doi:10.3389/fnbeh.2010.00179

Abstract

Disrupting reconsolidation of drug-related memories may be effective in reducing the incidence of relapse. In the current study we examine whether alcohol-related memories are prone to disruption by the β-adrenergic receptor antagonist propranolol (10 mg/kg) and the NMDA receptor antagonist MK801 (0.1 mg/kg) following their reactivation. In operant chambers, male Wistar rats were trained to self-administer a 12% alcohol solution. After 3 weeks of abstinence, the animals were placed in the self-administration cages and were re-exposed to the alcohol-associated cues for a 20-min retrieval period, immediately followed by a systemic injection of either propranolol, MK801 or saline. Rats were tested for cue-induced alcohol seeking on the following day. Retrieval session, injection and test were repeated on two further occasions at weekly intervals. Both propranolol and MK801 administration upon reactivation did not reduce alcohol seeking after the first reactivation test. However, a significant reduction of alcohol seeking was observed over three post-training tests in propranolol treated animals, and MK801 treated animals showed a strong tendency toward reduced alcohol seeking (p = 0.06). Our data indicate that reconsolidation of alcohol-related memories can be disrupted after a long post-training interval and that particularly β-adrenergic receptors may represent novel targets for pharmacotherapy of alcoholism, in combination with cue-exposure therapies.

Highlights

Alcohol consumption is socially accepted in many cultures
To what was seen in the reactivated condition repeated treatment without reactivation did not affect alcohol seeking [F(1,15) < 1, p > 0.80; Figure 2B], indicating that alcohol seeking behavior was not affected by home cage injections of propranolol
Using an operant alcohol self-administration model we demonstrate that (1) relatively old alcohol-related memories are prone to disruption in a reactivation-dependent manner and that (2) β-adrenoceptor mediated signaling is critically involved in reconsolidation of these memories

Summary

Introduction

Alcohol consumption is socially accepted in many cultures. The World Health Organization estimates that about 2 billion people regularly drink alcoholic beverages, 4% of whom have diagnosable alcohol use disorders. The economical, health, and domestic consequences of excessive alcohol use are a burden to society (WHO, 2004). Only few pharmacological treatments of alcohol dependence are available, and their effectiveness is limited (Anton et al, 2006). Environmental stimuli associated with the effects of self-administered drugs, including alcohol, are powerful sustainers of addictive behaviors and can precipitate relapse after prolonged periods of abstinence in both humans (O’Brien et al, 1998) and laboratory animals (De Vries et al, 2001; Chaudhri et al, 2008). Disrupting drug-associated memories could be an important new strategy for treating alcoholism and other addictive behaviors (Lee et al, 2005; Miller and Marshall, 2005; Diergaarde et al, 2008)

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Conclusion