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Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats

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Abstract

Rationale

Chronic opiate administration induces neuroadaptations within the nucleus accumbens (NAc) and ventral tegmental area (VTA) that can contribute to dependence. We have shown that morphine dependence shifts the behavioral consequences of D1 dopamine (DA) receptor signaling: systemic administration of a D1 receptor agonist is rewarding and blocks naloxone-precipitated withdrawal signs in morphine-dependent rats, but has minimal effects in nondependent rats. These data suggest that D1 receptors acquire the ability to regulate reward and withdrawal in morphine-dependent rats. The brain regions involved in these effects are not known.

Objective

Studies were designed to test the hypothesis that the nucleus accumbens shell (NASh) and the ventral tegmental area (VTA) are important sites for mediating the behavioral effects of D1 receptor activation in morphine-dependent rats.

Materials and methods

The effects of microinjecting the D1 receptor agonist SKF 82958 into the NASh or the VTA on place conditioning and somatic withdrawal signs were studied in morphine-dependent and nondependent rats.

Results

Intra-NASh microinjection of SKF 82958 (1 μg/side) established conditioned place preferences in morphine-dependent but not nondependent rats, but had no effect on naloxone-induced place aversions or somatic withdrawal signs. Intra-VTA microinjection of SKF 82958 (2 μg) did not establish place preferences under any conditions, but blocked naloxone-induced place aversions without effects on somatic withdrawal signs.

Conclusions

There is an anatomical dissociation between D1 receptor-mediated reward and relief of withdrawal in morphine-dependent rats. When combined, the individual effects of D1 receptor activation in the NASh and VTA on the affective signs of precipitated morphine withdrawal resemble those seen with systemic administration.

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Acknowledgements

This work was supported by National Institutes of Health grants DA012736 (to WC) and DA017524 (to EC) and conducted in a facility constructed with support from Research Facilities Improvement Program (RR11213) from the National Center for Research Resources.

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Authors and Affiliations

  1. Behavioral Genetics Laboratory, Department of Psychiatry, Harvard Medical School, McLean Hospital, MRC 218, 115 Mill Street, Belmont, MA, 02478, USA

    Elena H. Chartoff, Matthew F. Barhight, Steve D. Mague, Allison M. Sawyer & William A. Carlezon Jr.

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  1. Elena H. Chartoff
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  2. Matthew F. Barhight
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  3. Steve D. Mague
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  4. Allison M. Sawyer
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  5. William A. Carlezon Jr.
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Correspondence to Elena H. Chartoff.

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Chartoff, E.H., Barhight, M.F., Mague, S.D. et al. Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats. Psychopharmacology 204, 227–239 (2009). https://doi.org/10.1007/s00213-008-1454-7

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