Ethanol stimulation after chronic exposure in C57 mice

Middaugh, Lawrence D.; Favara, Jean P.; Boggan, William O.

doi:10.1016/0091-3057(89)90321-3

Cited by 10 publications

(4 citation statements)

References 13 publications

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“…and locomotor activity was recorded for 45 minutes. The ethanol dose and injection-test interval were chosen based on previous work (Fish et al 2002; Middaugh et al 1989). …”

Section: Methodsmentioning

confidence: 99%

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

et al. 2014

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Rationale Stress experiences have been shown to be a risk factor for alcohol abuse in humans; however, a reliable mouse model using episodic social stress has yet to be developed. Objectives The current studies investigated the effects of mild and moderate social defeat protocols on plasma corticosterone, voluntary alcohol drinking, and motivation to drink alcohol. Methods Outbred CFW mice were socially defeated for 10 days during which the intruder mouse underwent mild (15 bites: mean = 1.5 min), or moderate (30 bites: mean = 3.8 min) stress. Plasma corticosterone was measured on days 1 and 10 of the defeat. Ethanol drinking during continuous access to alcohol was measured 10 days following the defeat or 10 days prior to, during and 20 days after the defeat. Motivation to drink was determined using a PR operant conditioning schedule during intermittent access to ethanol. Results Plasma corticosterone was elevated in both stress groups on days 1 and 10. Ethanol consumption and preference following moderate social stress was higher than both the mild stress group and controls. Mice with previously acquired ethanol drinking showed decreased ethanol consumption during the moderate stress followed by an increase 20 days post-defeat. Moderately stressed mice also showed escalated ethanol intake (11g/kg/day) and ethanol self-administration during a schedule of intermittent access to alcohol. Conclusion Social defeat experiences of moderate intensity and duration led to increased ethanol drinking and preference in CFW mice. Ongoing work investigates the interaction between glucocorticoids and dopaminergic systems as neural mechanisms for stress-escalated alcohol consumption.

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“…and locomotor activity was recorded for 45 minutes. The ethanol dose and injection-test interval were chosen based on previous work (Fish et al 2002; Middaugh et al 1989). …”

Section: Methodsmentioning

confidence: 99%

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

et al. 2014

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“…In order to approximate the conditions of the first experiment in which mice were drinking ethanol in the 2 hr limited access paradigm, mice in experiment 2 were also given access to ethanol in the limited access paradigm for 3 weeks and experienced daily saline injections for habituation to the injection procedure. It should be noted that the stimulatory effects of EtOH in B6 mice have been observed whether mice are maintained with access to ethanol for consumption or not (Middaugh et al, 1992; Middaugh et al, 1987; Middaugh et al, 1989). After this period of EtOH drinking, on Monday and Thursday of each week, mice were exposed to the locomotor activity chambers for 20 minute sessions, but were not given access to ethanol for drinking.…”

Section: Methodsmentioning

confidence: 99%

“…Each condition was represented during each activity session except the first session in which all mice received vehicle injections in order to habituate them to the testing equipment. Injections were given five minutes prior to being placed into the chamber because this pretreatment interval consistently produces an increase in locomotor activity in C57BL/6J mice (Middaugh et al, 1992; Middaugh et al, 1987; Middaugh et al, 1989). The activity assessments occurred at the time when mice would have been given EtOH to drink in the limited access paradigm.…”

Section: Methodsmentioning

confidence: 99%

The interactive effects of methylphenidate and ethanol on ethanol consumption and locomotor activity in mice

Griffin¹,

Novak²,

Middaugh

et al. 2010

Pharmacology Biochemistry and Behavior

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The concomitant use of alcohol (EtOH) and the psychotherapeutic agent dl-methylphenidate (MPH) has risen as a consequence of an increase in ADHD diagnoses within the drinking age population. It was recently found that the combination of MPH and EtOH increases the self-report of pleasurable feelings relative to MPH alone. This finding raises concerns regarding the combined abuse liability for these two widely used drugs. The present behavioral study reports on the development of an adult male C57BL/6J (B6) mouse model to further characterize this MPH-EtOH interaction. We examined the effects of MPH on EtOH consumption in a limited access paradigm and EtOH stimulation of locomotor activity. B6 mice consumed about 2 g/kg EtOH daily and MPH dose-dependently reduced drinking. The most effective dose of MPH was 1.25 mg/kg, which produced a 41% decrease in drinking and had no effect on locomotor activity. However, when the 1.25 mg/kg dose of MPH was combined with a stimulatory dose of ethanol (1.75 g/kg) by intraperitoneal injection, there was a significantly enhanced stimulation of locomotor activity. The drug combination increased activity compared to the vehicle or MPH injections by 45% and increased the activity relative to EtOH alone by an additional 25%. The results of the EtOH and MPH interactions observed with the mouse model appear to be behaviorally relevant and suggest several converging mechanisms that may underlie MPH-EtOH interactions.

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“…The present set of experiments did provide evidence that the pharmacological effects of ethanol were enhanced by VGB. The biphasic action of ethanol, ranging from stimulation to depression of activity with increasing dose (Middaugh et al , 1989, 1992a,b), appeared to be shifted toward depression by administration of VGB. The stimulation produced by a 2 g/kg dose of ethanol, commonly observed in B6 mice, was attenuated by pretreatment with VGB 200 mg/kg (Figure 4), the dose most selective for reducing ethanol reinforcement.…”

Section: Discussionmentioning

confidence: 96%

Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice

Griffin¹,

Nguyen²,

Deleon³

et al. 2012

Behavioural Pharmacology

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We tested the hypothesis that the irreversible gamma-amino butyric acid (GABA) transaminase inhibitor, γ-vinyl GABA (Vigabatrin; VGB) would reduce ethanol reinforcement and enhance the discriminative stimulus effect of ethanol, effectively reducing ethanol intake. The present studies used adult C57BL/6J (B6) mice in well-established operant, two-bottle choice consumption, locomotor activity and ethanol discrimination procedures, to examine comprehensively the effects of VGB on ethanol-supported behaviors. VGB dose-dependently reduced operant responding for ethanol as well as ethanol consumption for long periods of time. Importantly, a low dose (200 mg/kg) of VGB was selective for reducing ethanol responding without altering intake of food or water reinforcement. Higher VGB doses (>200 mg/kg) still reduced ethanol intake, but also significantly increased water consumption and, more modestly, increased food consumption. While not affecting locomotor activity on its own, VGB interacted with ethanol to reduce the stimulatory effects of ethanol on locomotion. Finally, VGB (200 mg/kg) significantly enhanced the discriminative stimulus effects of ethanol as evidenced by significant left-ward and up-ward shifts in ethanol generalization curves. Interestingly, VGB treatment was associated with slight increases in blood ethanol concentrations. The reduction in ethanol intake by VGB appears to be related to the ability of VGB to potentiate the pharmacological effects of ethanol.

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Ethanol stimulation after chronic exposure in C57 mice

Cited by 10 publications

References 13 publications

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

Social stress and escalated drug self-administration in mice I. Alcohol and corticosterone

The interactive effects of methylphenidate and ethanol on ethanol consumption and locomotor activity in mice

Effects of vigabatrin, an irreversible GABA transaminase inhibitor, on ethanol reinforcement and ethanol discriminative stimuli in mice

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