Ethanol Drinking and Deprivation Alter Dopaminergic and Serotonergic Function in the Nucleus Accumbens of Alcohol-Preferring Rats

Abstract

The alcohol deprivation effect is a temporary increase in the intake of, or preference for, ethanol after a period of deprivation that may result from persistent changes in key limbic regions thought to regulate alcohol drinking, such as the nucleus accumbens. The present study tested the hypothesis that chronic alcohol drinking under continuous 24-h free-choice conditions alters dopamine and serotonin neurotransmission in the nucleus accumbens and that these alterations persist in the absence of alcohol. Using the no-net-flux microdialysis method, the steady-state extracellular concentration (point of no-netflux) for dopamine was approximately 25% higher in the adult female alcohol-preferring P rats given prior access to 10% ethanol, even after 2 weeks of ethanol abstinence, compared with the P rats gives access only to water. However, the extracellular concentration of serotonin was approximately 35% lower in animals given 8 weeks of continuous access to ethanol compared with water controls and animals deprived of ethanol for 2 weeks. The effect of local perfusion with 100 M sulpiride (D 2 receptor antagonist) and 35 M 1-(m-chlorophenyl)-biguanide (5-hydroxytryptamine 3 receptor agonist) on dopamine overflow were reduced approximately 33% in both groups of ethanol-exposed P rats compared with water controls. Freechoice alcohol drinking by P rats alters dopamine and serotonin neurotransmission in the nucleus accumbens, and many of these effects persist for at least 2 weeks in the absence of ethanol, suggesting that these underlying persistent changes may be in part responsible for increased ethanol drinking observed in the alcohol-deprivation effect.

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

“…Alternatively, persistent alterations (up to 2 weeks) in dopamine and serotonin neurotransmission in the nucleus accumbens of alcohol-preferring rats have been reported (Thielen et al, 2004). In this line, it has been proposed that the excessive and persistent increase in EtOH intake is caused by an elevation in the ethanol reward set point or threshold for ethanol reward, the allostasis hypothesis (Koob and Le Moal 1997;Roberts et al, 2000).…”

Ethanol, 3,4-Methylenedioxymethamphetamine (Ecstasy) and Their Combination: Long-Term Behavioral, Neurochemical and Neuropharmacological Effects in the Rat

“…Acute neurochemical and neuropharmacological effects of ethanol are well known, but especially compelling are the consequences after chronic intoxication or during withdrawal (eg Darstein et al, 2000;LeMarquand et al, 1994;Thielen et al, 2004). As to long-term effects of shorter periods of ethanol treatment, however, the literature is, to our knowledge, rather scanty.…”

Prolonged Increase in the Sensitivity of the Posterior Ventral Tegmental Area to the Reinforcing Effects of Ethanol following Repeated Exposure to Cycles of Ethanol Access and Deprivation

“…The increased sensitivity of the VTA to the reinforcing effects of ethanol are also in agreement with the findings of Brodie (2002), who reported that chronic alcohol drinking increased ethanolinduced excitation of DA neurons in the VTA. Chronic 24-h free-choice ethanol drinking by P rats was reported to reduce D 2 autoreceptor function and increase basal DA neurotransmission in the nucleus accumbens (Thielen et al, 2004). Therefore, it is possible that the higher sensitivity and number of ethanol infusions in the chronic alcohol-drinking group might be a result of higher DA neuronal activity in the VTA.…”

“…The development of tolerance to the non-reinforcing effects of ethanol may unmask the reinforcing effects of ethanol at other concentrations, resulting in increased sensitivity and higher self-infusions of ethanol at all concentrations. Alternatively, an explanation for a reduction in the non-reinforcing effects of ethanol with chronic ethanol exposure could be due to the higher basal level of DA neurotransmission observed in the nucleus accumbens of alcohol-drinking P rats (Thielen et al, 2004). The higher basal DA neuronal activity increases the sensitivity of the VTA to the reinforcing effects of ethanol and, at the same time, reduces the effects of the non-reinforcing high concentration of ethanol.…”

“…In addition, this study demonstrated that higher infusions of 50, 75, and 125 mg% were also found in the alcohol-drinking group, suggesting that prior alcohol drinking experience may have increased the reinforcing effects of ethanol within the posterior VTA. The increased sensitivity to the reinforcing effects of ethanol in the posterior VTA may be a result of higher basal DA neuronal activity in the nucleus accumbens of the chronic alcohol-drinking P rats (Thielen et al, 2004).…”