Oral ethanol self-administration in rats is reduced by the administration of dopamine and glutamate receptor antagonists into the nucleus accumbens

Abstract

The purpose of this study was to assess the role of endogenous dopamine and glutamate systems within the nucleus accumbens in modulating responses for oral ethanol reinforcements (10% w/v) in a free-choice operant task. Pretreatment with both systemic (100 micrograms/kg) and intra-nucleus accumbens microinjection of fluphenazine (2 and 4 micrograms), a dopamine receptor antagonist, significantly decreased responding for ethanol, without significantly affecting responses for water. Ethanol self-administration was also attenuated by microinjection into the nucleus accumbens of 2-amino-5-phosphopentanoic acid (AP-5, 3 and 6 micrograms), a competitive NMDA receptor antagonist. These results suggest that dopamine and glutamate neurotransmission in the nucleus accumbens may regulate ethanol self-administration and its reinforcing effects.

δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

“…Since there are DA-independent outputs of the VTA that can contribute to behavioral reinforcement (Nader and van der Kooy, 1997;Laviolette et al, 2004), it is possible that projecting glutamate or GABA VTA neurons are responsible for the modulation of drinking reported here. DA may also be involved in this modulation, since DA agonists and antagonists alter drinking (Pfeffer and Samson, 1988;Weiss et al, 1990;Rassnick et al, 1992Rassnick et al, , 1993Cohen et al, 1998Cohen et al, , 1999. If DA does play a role in DOR-mediated EtOH consumption, our data are consistent with an inverted u-shaped relationship between DA level and reward value.…”

Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo

“…Although the neurobiological systems that regulate ethanol self-administration remain to be fully characterized, it is widely accepted that the nucleus accumbens plays a role in this behavior (e.g., Hodge et al, 1995Hodge et al, , 1992Rassnick et al, 1992;Weiss et al, 1993). We previously showed that PKCε null mice self-administer less ethanol than wild-type controls and show no increase in dopamine levels in the nucleus accumbens after acute ethanol treatment (Olive et al, 2000), suggesting that PKC modulation of dopamine in this brain region may regulate ethanol self-administration.…”

The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

“…One important consideration is that Famous et al (2007) used a higher dose of AP5 (3 and 30 mg) to promote reinstated cocaine seeking, whereas Bäckström and Hyytiä (2007) found that lower doses of AP5 (1 and 2 mg) inhibit cue-induced cocaine seeking. Infusion of AP5 into the accumbens (no distinction made between the NAcore and NAshell) also decreases the potentiation of conditioned reinforcement caused by D-amphetamine (Burns et al, 1993) and decreases oral ethanol self-administration (Rassnick et al, 1992).…”