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A new model of the disrupted latent inhibition in C57BL/6J mice after bupropion treatment

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Abstract

Rationale

Schizophrenia is characterized by disturbances in attention and information processing that can be measured by latent inhibition (LI). Research has implicated significant aberrations in dopaminergic (DA) neurotransmission in this disorder.

Objectives

The objectives of this study were as follows: to probe whether bupropion disrupts LI; to compare its efficacy to the effects of GBR12783 (specific DA uptake inhibitor) and to amphetamine (DA releaser); to test if antipsychotics would reverse LI deficits induced by bupropion, GBR12783, and amphetamine; and to probe if rolipram (phosphodiesterase-4 inhibitor), which increases cyclic AMP (cAMP) similarly to antipsychotics, effectively corrects drug-induced LI deficits. Based on its efficacy in drug addiction, we also asked if bupropion could block the effect of amphetamine.

Methods

LI was measured in a conditioned emotional response procedure by comparing suppression of drinking in response to a noise in C57BL/6J mice. Mice previously received 0 (nonpreexposed) or 40 noise exposures (preexposed) followed by two or four noise-foot shock pairings.

Results

Bupropion abolished LI in mice, which was corrected by rolipram, but not by haloperidol and clozapine. GBR12783 and amphetamine, but not antidepressants, also disrupted LI, and this was reversed by antipsychotics and rolipram. Both bupropion and amphetamine disrupted LI via conditioning session. Paradoxically, bupropion and GBR12783 also blocked the amphetamine-induced LI deficit.

Conclusions

Efficacy of rolipram but not antipsychotics to reverse the effects of bupropion suggests novel cAMP-dependent and D2 receptor-independent mechanisms of the bupropion-induced LI deficit. Further detailed biochemical analysis of bupropion-induced LI deficit might be a fruitful approach in developing new antipsychotics.

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Acknowledgments

Funding was provided by the Ontario Mental Health Foundation (OMHF) and the Canadian Institutes of Health Research (CIHR). We thank Professor Ina Weiner for helpful discussion of the data.

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  1. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, Canada, M5G 1X5

    Tatiana Lipina & John Roder

  2. Program in Neuroscience, University of Toronto, Toronto, ON, Canada

    John Roder

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  1. Tatiana Lipina
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Correspondence to Tatiana Lipina.

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Lipina, T., Roder, J. A new model of the disrupted latent inhibition in C57BL/6J mice after bupropion treatment. Psychopharmacology 208, 487–498 (2010). https://doi.org/10.1007/s00213-009-1749-3

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