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The involvement of type IV phosphodiesterases in cocaine-induced sensitization and subsequent pERK expression in the mouse nucleus accumbens

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Abstract

Rationale

Cocaine exposure produces sensitization that is partly mediated by cyclic adenosine monophosphate (cAMP) pathways within the nucleus accumbens (NAc). Type IV phosphodiesterases (PDE4s) break down cAMP and are required for cocaine-induced conditioned place preference. Whether PDE4 disruption attenuates induction of behavioral sensitization to cocaine and subsequent NAc expression of phosphorylated extracellular signal-regulated kinase (ERK), which is involved in cocaine-induced sensitization, is unknown.

Objectives

The objective of this study was to determine whether inhibition of PDE4s prevents cocaine-induced locomotor sensitization and if reduced behavioral sensitization is accompanied by decreased expression of phosphorylated ERK (pERK) within the NAc.

Methods

Mice were administered the PDE4 inhibitor, rolipram, or vehicle before or after five daily injections of cocaine or saline, and activity was monitored on days 1 and 5. After nine drug-free days, locomotor sensitization was tested. Some subjects were sacrificed following testing for behavioral sensitization to measure pERK expression in the NAc.

Results

PDE4 inhibition, during the induction of sensitization, reduced behavioral sensitization only if rolipram (1.0 mg/kg) was administered before cocaine. Re-exposure to the cocaine-paired environment following a 9-day drug-free period enhanced pERK expression in the NAc core and shell. Rolipram did not alter pERK induction despite blocking behavioral sensitization.

Conclusions

Rolipram given during, but not following, cocaine treatment prevents development of locomotor sensitization to cocaine but does not affect subsequent pERK activation induced by exposure to a cocaine-paired context or following a cocaine challenge. Although PDE4 inhibition during the induction of sensitization blocks the locomotor component of sensitization, other long-term changes induced by repeated cocaine treatment remain.

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Authors and Affiliations

  1. Department of Psychology, Boston University, Boston, MA, 02215, USA

    Amy C. Janes, Kathleen M. Kantak & James A. Cherry

  2. Brain Imaging Center, McLean Hospital, 115 Mill St, Belmont, MA, 02478, USA

    Amy C. Janes

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  1. Amy C. Janes
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  2. Kathleen M. Kantak
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  3. James A. Cherry
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Correspondence to Amy C. Janes.

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Janes, A.C., Kantak, K.M. & Cherry, J.A. The involvement of type IV phosphodiesterases in cocaine-induced sensitization and subsequent pERK expression in the mouse nucleus accumbens. Psychopharmacology 206, 177–185 (2009). https://doi.org/10.1007/s00213-009-1594-4

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  • DOI: https://doi.org/10.1007/s00213-009-1594-4

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