Recent advances in animal models of alcohol craving and relapse

Rodd, Zachary A.; Bell, Richard L.; Sable, Helen J.K.; Murphy, James M.; McBride, William J.

doi:10.1016/j.pbb.2004.08.018

Cited by 142 publications

(133 citation statements)

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“…alcohol administration (eg Lopez and Becker, 2005;Melendez et al, 2006;Roberts et al, 2000;Valdez et al, 2002; for reviews, Rodd et al, 2004;Spanagel, 2000) and indicate that an alcohol-induced increase in NAC Homer2b expression is sufficient to 'presensitize' B6 mice to alcohol's rewarding and reinforcing properties. The effects of manipulating Homer expression upon alcohol reward do not likely reflect changes in general reward mechanisms as little evidence supports a role for Homer2 isoforms in regulating food or water reward.…”

Section: Accumbens Homer2b Upregulation Promotes Alcohol Rewardmentioning

confidence: 99%

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

Szumlinski

Ary

Lominac

et al. 2007

Neuropsychopharmacol

178

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Homer proteins are integral components of the postsynaptic density that are necessary for alcohol-induced neuroplasticity within the nucleus accumbens (NAC). In this report, we describe the effects of chronic alcohol consumption upon NAC Homer expression and investigate the functional consequences of mimicking the alcohol-induced changes in Homer expression vis-à-vis alcohol-induced changes in NAC neurochemistry and behavior. Chronic alcohol consumption under continuous access (3 months; daily intake E11.271.5 g/kg/ day) produced a robust increase in NAC Homer2 protein levels that was apparent at 2 days, 2 weeks, and 2 months following withdrawal from alcohol drinking. The increased Homer2 expression was accompanied by a less enduring elevation in total mGluR1 and NR2b levels that were evident at 2 days and 2 weeks but not at the 2-month time point. Mimicking the alcohol-induced increase in Homer2 levels by viral transfection of NAC neurons in alcohol-preferring C57BL/6J inbred mice enhanced behavioral output for alcohol reinforcement and increased alcohol intake under both preprandial and postprandial conditions. Moreover, NAC Homer2 overexpression facilitated the expression of an alcohol-conditioned place preference, as well as the development of motor tolerance. Finally, NAC Homer2 overexpression facilitated NAC glutamate and dopamine release following an acute alcohol injection and augmented alcohol-induced dopamine and glutamate sensitization, but did not affect NAC g-aminobutyric acid levels. Thus, an upregulation in NAC mGluR-Homer2-N-methyl-D-aspartic acid receptor signaling appears to be an important molecular adaptation to alcohol that promotes neuroplasticity facilitating motivational drive for alcohol and the development of alcoholism-related behaviors.

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Section: Accumbens Homer2b Upregulation Promotes Alcohol Rewardmentioning

confidence: 99%

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

Szumlinski

Ary

Lominac

et al. 2007

Neuropsychopharmacol

178

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“…Given that relapse is a major obstacle in the treatment of alcohol addiction, attention has been focused on animal models to further our understanding of alcohol relapse and craving (Koob, 2000;Spanagel, 2003;Rodd et al, 2004b).…”

Section: Introductionmentioning

confidence: 99%

The Posterior Ventral Tegmental Area Mediates Alcohol-Seeking Behavior in Alcohol-Preferring Rats

Hauser

Ding

Getachew

et al. 2010

J Pharmacol Exp Ther

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The mesolimbic dopamine (DA) system is involved in the rewarding process of drugs of abuse and is activated during the anticipation of drug availability. However, the neurocircuitry that regulates ethanol (EtOH)-seeking has not been adequately investigated. The objectives of the present study were to determine 1) whether the posterior ventral tegmental area (p-VTA) mediates EtOH-seeking, 2) whether microinjections of EtOH into the p-VTA could stimulate EtOH-seeking, and (3) the involvement of p-VTA DA neurons in EtOH-seeking. Alcoholpreferring rats were trained to self-administer 15% EtOH and water. After 10 weeks, rats underwent extinction training, followed by 2 weeks in their home cages. During the home-cage period, rats were then bilaterally implanted with guide cannulae aimed at the p-VTA or anterior ventral tegmental area (a-VTA).EtOH-seeking was assessed by the Pavlovian spontaneous recovery model. Separate experiments examined the effects of: 1) microinjection of quinpirole into the p-VTA, 2) EtOH microinjected into the p-VTA, 3) coadministration of EtOH and quinpirole into the p-VTA, 4) microinjection of quinpirole into the a-VTA, and 5) microinjection of EtOH into the a-VTA. Quinpirole microinjected into the p-VTA reduced EtOH-seeking. Microinjections of EtOH into the p-VTA increased EtOH-seeking. Pretreatment with both quinpirole and EtOH into the p-VTA reduced EtOH-seeking. Microinjections of quinpirole or EtOH into the a-VTA did not alter EtOH-seeking. Overall, the results suggest that the p-VTA is a neuroanatomical substrate mediating alcohol-seeking behavior and that activation of local DA neurons is involved.

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“…The P rat satisfies the criteria proposed as essential for an animal model of alcoholism (Cicero, 1979;Lester and Freed, 1973). This line of rats voluntarily consumes EtOH for its pharmacological effects, attains blood alcohol levels from 50 − 200 mg%, will work to obtain EtOH, and develops tolerance and dependence through free-choice alcohol drinking (reviewed in Murphy et al 2002;Rodd et al, 2004). McBride and Li (1998) expanded on this model, further suggesting that an animal model of alcoholism should display characteristics associated with relapse, as research has shown that the drinking patterns of human alcoholics have multiple periods of abstinence and intake (Burish et al, 1981;Hilbrom, 1990;McMillen, 1997).…”

Section: Introductionmentioning

confidence: 99%

“…Operant techniques, examining alterations in the amount of work a subject will do to obtain a reinforcement, can be used to examine the effects of repeated deprivations on the reinforcing properties of EtOH, effectively modeling relapse (Ciccocioppo et al, 2001;Hodos, 1961;Rodd et al, 2004). Specifically, the deprivation effect, a temporary increase in a particular reward-seeking behavior seen after absence of the reward, can illuminate relapse-like behavior.…”

Section: Introductionmentioning

confidence: 99%

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Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats

Toalston

Oster

Kuc

et al. 2008

Alcohol

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Consumption of sweet solutions has been associated with a reduction in withdrawal symptoms and alcohol craving in humans. The objective of the present study was to determine the effects of EtOH and saccharin (SACC) deprivations on operant oral self-administration. P rats were allowed to lever press concurrently self-administer EtOH (15% v/v) and SACC (0.0125% g/v) for 8 weeks. Rats were then maintained on daily operant access (non-deprived), deprived of both fluids (2 weeks), deprived of SACC and given 2 ml of EtOH daily, or deprived of EtOH and given 2 ml of SACC daily. All groups were then given two weeks of daily operant access to EtOH and SACC, followed by an identical second deprivation period. P rats responded more for EtOH than SACC. All deprived groups increased responding on the EtOH lever, but not on the SACC lever. Daily consumption of 2 ml EtOH decreased the duration of the ADE. Home cage access to 2 ml SACC also decreased the ADE but to a lesser extent than access to EtOH. A second deprivation period further increased and prolonged the expression of an ADE. These results show EtOH is a more salient reinforcer than SACC. With concurrent access to EtOH and SACC, P rats do not display a saccharin deprivation effect. Depriving P rats of both EtOH and SACC had the most pronounced effect on the magnitude and duration of the ADE, suggesting that there may be some interactions between EtOH and SACC in their CNS reinforcing effects.

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Recent advances in animal models of alcohol craving and relapse

Cited by 142 publications

References 100 publications

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

Accumbens Homer2 Overexpression Facilitates Alcohol-Induced Neuroplasticity in C57BL/6J Mice

The Posterior Ventral Tegmental Area Mediates Alcohol-Seeking Behavior in Alcohol-Preferring Rats

Effects of alcohol and saccharin deprivations on concurrent ethanol and saccharin operant self-administration by alcohol-preferring (P) rats

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