Ethanol Reinforcement in Nondeprived Mice: Effects of Abstinence and Naltrexone

Middaugh, Lawrence D.; Lee, Allison M.; Bandy, Angela‐Leigh E.

doi:10.1097/00000374-200008000-00006

Cited by 19 publications

(32 citation statements)

References 34 publications

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“…Instrumental response training was conducted with modifications to previously described procedures [23]. Mice were initially trained to consume a 0.2% w/v saccharin solution (0.2S) from a retractable sipper during two 20-min trials per day for 7 days.…”

Section: Sipper and Lever Acquisition Training Phasesmentioning

confidence: 99%

“…A modified saccharin fading procedure was used to initiate ethanol self-administration [23,35]. Briefly, the ethanol concentration was increased within the 0.2S solution [for two sessions each at 0.2% saccharin/3% ethanol (0.2S/3E), 0.2S/6E, 0.2S/9E, and 0.2S/12E], and then saccharin was subsequently faded out in a step-wise manner to yield a 10% v/v ethanol (10E) solution [for 5 sessions each at 0.1S/12E, 0.05S/12E, 0.025S/12E, 0.01S/12E, and then 10E].…”

Section: Saccharin Fading Procedures and Reinforcement Schedule Manipumentioning

confidence: 99%

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Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Ford

Mark

Nickel

et al. 2007

Behavioural Brain Research

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Although systemic allopregnanolone (ALLO; a positive modulator of GABA A receptors) has been shown to enhance ethanol-reinforced responding and to modulate drinking patterns in rodents, the effects of centrally administered ALLO on ethanol intake are not known. The current work examined the effects of intracranial ALLO on operant ethanol self-administration in food-and water-satiated mice, with a procedure designed to estimate ALLO's influence on appetitive versus consummatory processes. Male C57BL/6J (B6) mice were trained to press an ethanol-appropriate lever by being reinforced with 30-min of continuous access to a 10% ethanol solution. Following surgical implantation of a guide cannula aimed at the lateral ventricle and subsequent habituation to vehicle infusions, ALLO (50-400 ng; ICV) was delivered immediately prior to session start. ALLO doses of 100 and 400 ng were further evaluated for their effects on locomotor behavior within activity chambers. ALLO selectively modulated ethanol intake patterns associated with the onset and maintenance of self-administration, while leaving appetitive (i.e., ethanol seeking) measures unaltered. The effects of ALLO on drinking patterns were dissociable from changes in locomotor behavior, as evidenced by the absence of ALLO's influence on response frequency and horizontal distance traveled. These findings support the premise that manipulations in brain ALLO levels may influence the regulatory processes governing ethanol consumption.

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Section: Sipper and Lever Acquisition Training Phasesmentioning

confidence: 99%

Section: Saccharin Fading Procedures and Reinforcement Schedule Manipumentioning

confidence: 99%

Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Ford

Mark

Nickel

et al. 2007

Behavioural Brain Research

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“…A modified saccharin fading procedure was utilized to initiate ethanol self-administration (Czachowski et al, 2001;Middaugh et al, 2000;Samson, 1986). Throughout saccharin fading, mice were maintained on a FR1 reinforcement schedule for 15-sec sipper access periods during 30-min sessions.…”

Section: Saccharin Fading Procedures and Reinforcement Schedule Manipumentioning

confidence: 99%

“…Although the reinforcing effects of ethanol have been successfully demonstrated when the drug is continuously available (Besheer et al, 2004;Hodge et al, 2006;Olive et al, 2000;Risinger et al, 1998Risinger et al, ,1999, data evaluating ethanol reinforcement in mice under a limited access condition is less well studied. Studies with mice responding on a fixed ratio 1 (FR1) (Middaugh et al 2000;Roberts et al 2000) or FR3 (Tsiang and Janak, 2006) reinforcement schedule reported ethanol intake approximating 0.5 g/kg, which correspond to values in rats responding on a FR schedule (e.g., Samson, 2000).…”

Section: Introductionmentioning

confidence: 99%

Influence of reinforcement schedule on ethanol consumption patterns in non-food restricted male C57BL/6J mice

Ford

Fretwell²,

Mark

et al. 2007

Alcohol

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Ethanol reinforcement should ideally be evaluated in animals that are not food deprived to ensure that the motivation behind its consumption is pharmacological, and not caloric, in nature. The objective of this work was to assess the influence of reinforcement schedule on ethanol intake in non-deprived mice. Male C57BL/6J mice were trained to respond on an ethanol-reinforced lever on a fixed ratio (FR) 4 reinforcement schedule for 10% ethanol (10E). The appetitive and consummatory phases were then procedurally separated by changing the response requirement (RR), so that mice were permitted 30-min continuous 10E access after completion of either four (RR4) or eight (RR8) responses. Phase separation yielded a heightened appetitive drive to acquire 10E access (as indexed by a significant decrease in the latency to first active lever and a trend towards a decrease in the latency to 1st sipper contact) and an augmented level of drinking (2-fold elevation in the ethanol dose consumed). Robust extinction responding on the ethanol-appropriate lever indicated that ethanol was effective as a behavioral reinforcer. These results suggest that the separation of appetitive and consummatory phases of ethanol self-administration may prove useful in future evaluations of the pharmacological and genetic bases of ethanol reinforcement in mice.

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“…When mice and rats have limited access to an ethanol solution with either 2-bottle choice (e.g., Finn et al, 2004;Ford et al, 2005;Grahame et al, 1999;Li et al, 1993;McBride and Li, 1998) or operant (e.g., Backstrom and Hyytia¨2005; Czachowski et al, 2002;Elmer et al, 1987;Funk et al, 2005;Middaugh et al, 2000;O'Dell et al, 2005;Risinger et al, 1998;Roberts et al, 2000;Tsiang and Janak, 2006) procedures, they can reliably selfadminister doses of alcohol that are believed to be pharmacologically active.…”

mentioning

confidence: 99%

Increased Drinking During Withdrawal From Intermittent Ethanol Exposure Is Blocked by the CRF Receptor Antagonist d‐Phe‐CRF(12–41)

Finn

Snelling

Fretwell

et al. 2007

Alcoholism Clin & Exp Res

191

182

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Background: Studies in rodents have determined that intermittent exposure to alcohol vapor can increase subsequent ethanol self-administration, measured with operant and 2-bottle choice procedures. Two key procedural factors in demonstrating increased alcohol intake are the establishment of stable alcohol self-administration before alcohol vapor exposure and the number of bouts of intermittent vapor exposure. The present studies provide additional behavioral validation and initial pharmacological validation of this withdrawal-associated drinking procedure.Methods: Studies at 2 different sites (Portland and Scripps) examined the effect of intermittent ethanol vapor exposure (3 cycles of 16 hours of ethanol vapor18 hours air) on 2-hour limited access ethanol preference drinking in male C57BL/6 mice. Separate studies tested 10 or 15% (v/v) ethanol concentrations, and measured intake during the circadian dark. In one study, before measuring ethanol intake after the second bout of intermittent vapor exposure, mice were tested for handlinginduced convulsions (HICs) indicative of physical dependence on ethanol. In a second study, the effect of bilateral infusions of the corticotropin-releasing factor (CRF) receptor antagonist D-Phe-CRF(12-41) (0.25 mg/0.5 mL) into the central nucleus of the amygdala (CeA) on ethanol intake was compared in vapor-exposed animals and air controls.Results: Intermittent ethanol vapor exposure significantly increased ethanol intake by 30 to 40%, and the mice had higher blood ethanol concentrations than controls. Intra-amygdala infusions of D-Phe-CRF(12-41) significantly decreased the withdrawal-associated increase in ethanol intake without altering ethanol consumption in controls. Following the second bout of intermittent vapor exposure, mice exhibited an increase in HICs, when compared with their own baseline scores or the air controls.Conclusions: Intermittent alcohol vapor exposure significantly increased alcohol intake and produced signs of physical dependence. Initial pharmacological studies suggest that manipulation of the CRF system in the CeA can block this increased alcohol intake.

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Ethanol Reinforcement in Nondeprived Mice: Effects of Abstinence and Naltrexone

Abstract: Ethanol appears to serve as a reinforcer for non-food-deprived or non-water-deprived B6 mice. Its reinforcing effects are increased by forced abstinence after chronic exposure and are decreased by naltrexone.

Cited by 19 publications

References 34 publications

Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Allopregnanolone influences the consummatory processes that govern ethanol drinking in C57BL/6J mice

Influence of reinforcement schedule on ethanol consumption patterns in non-food restricted male C57BL/6J mice

Increased Drinking During Withdrawal From Intermittent Ethanol Exposure Is Blocked by the CRF Receptor Antagonist d‐Phe‐CRF(12–41)

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