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The role of endogenous PACAP in motor stimulation and conditioned place preference induced by morphine in mice

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Abstract

Rationale

The neuropeptide pituitary adenylyl cyclase-activating peptide (PACAP) and its receptors (PAC1 and VPAC2) are expressed in the ventral tegmental area and nucleus accumbens, raising the possibility that PACAP could be a potential modulator of the mesolimbic dopaminergic system.

Objective

The present study was designed to determine if PACAP plays a role in acute motor stimulatory and rewarding actions of morphine.

Methods

The effect of intracerebroventricular PACAP administration (0, 0.03, 0.3, 1.0, or 3.0 μg/3 μL) was studied on basal motor activity as well as on morphine (5 mg/kg)-stimulated motor activity. Motor stimulation and conditioned place preference (CPP) induced by morphine (5 or 10 mg/kg) were also determined in mice lacking PACAP and their wild-type controls.

Results

Intracerebroventricular PACAP dose-dependently suppressed basal motor activity and PACAP-deficient mice exhibited higher basal motor activity than control mice, providing evidence that the action of endogenous PACAP on basal motor activity is inhibitory. Paradoxically, low doses of PACAP which did not alter basal motor activity were found to enhance the motor stimulatory action of morphine. Furthermore, morphine-induced motor stimulation was blunted in PACAP-deficient mice. Additionally, morphine-induced CPP following a single, but not repeated, alternate-day saline/morphine (10 mg/kg) conditioning was blunted in PACAP-deficient mice compared to their wild-type littermates/controls.

Conclusion

The present results suggest that endogenous PACAP, at low doses, positively modulates the acute motor stimulatory and rewarding actions of morphine.

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Acknowledgements

The authors wish to thank Mr. Rishi Talwar for technical assistance. This work was supported in part by the State of California funds for medical research on alcohol and substance abuse through the University of California, San Francisco and in part by National Institutes of Health grants HD06576, HD34475, and HD0461 and (J.A.W.), DA05010 (C.J.E.), DA016682, and an intramural grant at Western University of Health Sciences (K.L.)

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Western University of Health Sciences, 309 East 2nd Street, Pomona, CA, 91766, USA

    Paul Marquez, David Bebawy & Kabirullah Lutfy

  2. Department of Psychiatry and Biobehavioral Sciences, Neuropsychiatric Institute, David Geffen School of Medicine, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA, 90024, USA

    Vincent Lelièvre, Anne-Claire Coûté, Christopher J. Evans & James A. Waschek

  3. Mental Retardation Research Center, University of California, Los Angeles, 760 Westwood Plaza, Los Angeles, CA, 90024, USA

    Vincent Lelièvre, Anne-Claire Coûté & James A. Waschek

Authors
  1. Paul Marquez
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  2. David Bebawy
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  3. Vincent Lelièvre
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  4. Anne-Claire Coûté
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  5. Christopher J. Evans
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  6. James A. Waschek
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  7. Kabirullah Lutfy
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Correspondence to Kabirullah Lutfy.

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Marquez, P., Bebawy, D., Lelièvre, V. et al. The role of endogenous PACAP in motor stimulation and conditioned place preference induced by morphine in mice. Psychopharmacology 204, 457–463 (2009). https://doi.org/10.1007/s00213-009-1476-9

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  • DOI: https://doi.org/10.1007/s00213-009-1476-9

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