Behavioral sensitization to ethanol is modulated by environmental conditions, but is not associated with cross-sensitization to allopregnanolone or pentobarbital in DBA/2J mice

doi:10.1016/j.neuroscience.2004.11.005

Neuroscience

Volume 131, Issue 2, 2005, Pages 263-273

https://doi.org/10.1016/j.neuroscience.2004.11.005 Get rights and content

Abstract

Rationale: The ability of ethanol to facilitate GABA_A receptor-mediated transmission may result in GABA_A receptor alterations during repeated ethanol administration, and lead to dynamic behavioral changes, including sensitization to the locomotor stimulant effect of ethanol. Since alterations in GABA_A receptors are likely to alter sensitivity to GABAergic drugs such as 3α-hydroxy-5α-pregnan-20-one (allopregnanolone) and pentobarbital, we determined whether enhanced sensitivity to ethanol was associated with enhanced sensitivity (cross-sensitization) to these drugs. Two procedures that produced differences in the magnitude of expression of ethanol-induced locomotor sensitization were used.

Methods

After habituation to testing procedures for 2 days, female DBA/2J mice were injected with ethanol or saline for 12 days. On the following day, locomotion was recorded after a challenge injection of ethanol (2 g/kg), allopregnanolone (10 or 17 mg/kg), or pentobarbital (10 or 20 mg/kg). Due to evidence that exposure to the test chambers influenced sensitization, in some experiments, mice were exposed to the test apparatus on the day prior to challenge.

Results

Exposure to the test apparatus prior to drug challenge attenuated the expression of ethanol sensitization, compared with mice without this pre-exposure. Cross-sensitization was not observed to either allopregnanolone or pentobarbital under any condition; however, some groups of repeated ethanol-treated mice displayed tolerance to the initial stimulant effects of allopregnanolone and pentobarbital.

Conclusions

These studies indicate that behavioral sensitization to ethanol is not associated with cross-sensitization to pentobarbital or allopregnanolone, and that the expression of ethanol sensitization is influenced by the relative novelty of the test chamber. In addition, these results do not support a mechanism in which alterations in the neurosteroid or barbiturate modulatory sites of the GABA_A receptor are responsible for the expression of sensitization to the locomotor stimulant effects of ethanol.

Section snippets

Subjects and housing

Female DBA/2J mice were purchased from The Jackson Laboratory (Bar Harbor, ME, USA), and allowed to adapt to the Veterans Affairs Medical Center animal research facility for at least 1 week prior to the initiation of testing. This strain of mice was chosen for its susceptibility to ethanol-induced behavioral sensitization (Phillips et al., 1995). Females were chosen for consistency with our previous work (Phillips et al., 1992, 1995), and because others have found that female rodents displayed

Experiment 1

There were differences in locomotor activity across days 1 through 14 for the repeated ethanol- and saline-treated mice [Fig. 1A; F(3,132)=98.4; P<0.01, for the Repeated Treatment×Day interaction]. Simple main effects analyses followed by planned comparisons revealed that the ethanol-treated mice expressed significant behavioral sensitization on day 14 (P<0.01), compared with day 3. There was no change in the response to saline on day 14 compared with day 3 in the saline-treated mice. As can be

Discussion

The present results demonstrate robust behavioral sensitization to the locomotor stimulant effects of ethanol, as has previously been reported for DBA/2J mice (Broadbent and Harless, 1999; Cunningham and Noble, 1992; Lessov et al., 2001a,b; Phillips et al., 1994; Roberts et al., 1995). Further, the results show a lack of cross-sensitization between ethanol and either allopregnanolone or pentobarbital, both of which are thought to produce their effects via interactions with specific modulatory

Acknowledgments

This work was supported by NIAAA grants P50AA10760, T32AA07468 and F32AA05600, as well as a grant from the Department of Veterans Affairs. All of these procedures comply with the current laws of the United States of America and were performed in accordance with the Institutional Animal Care and Use Committee and National Institutes of Health guidelines for the care and use of laboratory animals.

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¹: Present address: Columbia Genome Center, Columbia University, New York, NY, USA.

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Behavioral sensitization to ethanol is modulated by environmental conditions, but is not associated with cross-sensitization to allopregnanolone or pentobarbital in DBA/2J mice

Abstract

Methods

Results

Conclusions

Section snippets

Subjects and housing

Experiment 1

Discussion

Acknowledgments

Pharmacol Biochem Behav

Brain Res

Prog Brain Res

Eur J Pharmacol

Pharmacol Biochem Behav

Behav Brain Res

Trends Pharmacol Sci

Pharmacol Biochem Behav

Physiol Behav

Pharmacol Biochem Behav

Pharmacol Biochem Behav

Neuroscience

Neuropsychopharmacology

Neuroscience

Neuropharmacology

Pharmacol Biochem Behav

Brain Res

Pharmacol Biochem Behav

Neuropsychopharmacology

Eur J Pharmacol

Pharmacol Ther

Alcohol

Pharmacol Biochem Behav

Eur J Pharmacol

Brain Res Rev

Compr Psychiatry

FEBS Lett

Eur J Pharmacol

Modulation of morphine sensitization in the rat by contextual stimuli

Psychopharmacology

Gender differences in the behavioral responses to cocaine and amphetamineimplications for mechanisms mediating gender differences in drug abuse

Ann NY Acad Sci

Differential effects of GABA(A) and GABA(B) agonists on sensitization to the locomotor stimulant effects of ethanol in DBA/2 J mice

Psychopharmacology

Dizocilpine (MK-801) prevents the development of sensitization to ethanol in DBA/2J mice

Alcohol Alcohol

Haloperidol prevents ethanol-stimulated locomotor activity but fails to block sensitization

Psychopharmacology

Expression of behavioral sensitization to ethanol by DBA/2J micethe role of NMDA and non-NMDA glutamate receptors

Psychopharmacology

Benzodiazepine agonist and inverse agonist actions on GABAA receptor-operated chloride channels: I. Acute effects of ethanol

J Pharmacol Exp Ther

Benzodiazepine agonist and inverse agonist actions on GABAA receptor-operated chloride channels: II. Chronic effects of ethanol

J Pharmacol Exp Ther

MK-801 blocks the development of behavioral sensitization to the ethanol

Alcohol Clin Exp Res

Involvement of the opioid system in the development and expression of sensitization to the locomotor-activating effect of ethanol

Int J Neuropsychopharmacol

Effects of acamprosate on sensitization to the locomotor-stimulant effects of alcohol in mice selectively bred for high and low alcohol preference

Behav Pharmacol

Cocaine sensitization and cravingdiffering roles for dopamine and glutamate in the nucleus accumbens

J Addict Dis

Locomotor stimulant effects of intraventricular injections of low doses of ethanol in ratsacute and repeated administration

Psychopharmacology

Genetic determinants of sensitivity to pentobarbital in inbred mice

Psychopharmacology