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Alcohol-induced retrograde memory impairment in rats: prevention by caffeine

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Abstract

Rationale

Ethanol and caffeine are two of the most widely consumed drugs in the world, often used in the same setting. Animal models may help to understand the conditions under which incidental memories formed just before ethanol intoxication might be lost or become difficult to retrieve.

Objectives

Ethanol-induced retrograde amnesia was investigated using a new odor-recognition test.

Materials and methods

Rats thoroughly explored a wood bead taken from the cage of another rat, and habituated to this novel odor (N1) over three trials. Immediately following habituation, rats received saline, 25 mg/kg pentylenetetrazol (a seizure-producing agent known to cause retrograde amnesia) to validate the test, 1.0 g/kg ethanol, or 3.0 g/kg ethanol. The next day, they were presented again with N1 and also a bead from a new rat’s cage (N2).

Results

Rats receiving saline or the lower dose of ethanol showed overnight memory for N1, indicated by preferential exploration of N2 over N1. Rats receiving pentylenetetrazol or the higher dose of ethanol appeared not to remember N1, in that they showed equal exploration of N1 and N2. Caffeine (5 mg/kg), delivered either 1 h after the higher dose of ethanol or 20 min prior to habituation to N1, negated ethanol-induced impairment of memory for N1. A combination of a phosphodiesterase-5 inhibitor and an adenosine A2A antagonist, mimicking two major mechanisms of action of caffeine, likewise prevented the memory impairment, though either drug alone had no such effect. Binge alcohol can induce retrograde, caffeine-reversible disruption of social odor memory storage or recall.

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Acknowledgments

The authors would like to thank John Heymann and Whitney O’Connell for their indispensable contributions to the experimental design and tireless efforts with regard to behavioral testing. This work was supported by NIH grants NS19608, HD02023, and NS042345.

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Authors and Affiliations

  1. Department of Psychology, The University of Texas at Austin, 1 University Station, #A8000, Austin, TX, 78712, USA

    Michael J. Spinetta, Leila M. Feinberg, Lawrence K. Cormack & Timothy Schallert

  2. Institute for Neuroscience, The University of Texas at Austin, Austin, TX, USA

    Martin T. Woodlee, Lawrence K. Cormack & Timothy Schallert

  3. Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX, USA

    Chris Stroud & Kellan Schallert

  4. Department of Neurosurgery, University of Michigan, Ann Arbor, MI, USA

    Timothy Schallert

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  1. Michael J. Spinetta
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  2. Martin T. Woodlee
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Correspondence to Timothy Schallert.

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Spinetta, M.J., Woodlee, M.T., Feinberg, L.M. et al. Alcohol-induced retrograde memory impairment in rats: prevention by caffeine. Psychopharmacology 201, 361–371 (2008). https://doi.org/10.1007/s00213-008-1294-5

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  • DOI: https://doi.org/10.1007/s00213-008-1294-5

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