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Prior, repeated exposure to cocaine potentiates locomotor responsivity to central injections of corticotropin-releasing factor (CRF) in rats

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Abstract

Rationale

There is considerable evidence that the stress-related neuropeptide, corticotropin-releasing factor (CRF), plays an important role in mediating behavioural changes induced by prior experience with cocaine. From this perspective, it is conceivable that repeated exposure to cocaine induces a form of sensitization in CRF systems that makes animals more responsive to CRF following prolonged drug-free periods.

Objectives

To study the effects of repeated cocaine exposure on locomotor activity induced by different doses of CRF after drug-free periods ranging from 24 h to 28 days.

Methods

Male Wistar rats were injected once daily for 7 days with cocaine (15 mg/kg, IP on days 1 and 7 in locomotor chambers; 30 mg/kg, IP, on days 2–6 in home cages) or saline. In experiment 1, starting 10 days after the last injection, animals were tested for their locomotor response to intracerebroventricular (ICV) injections of vehicle and three doses of CRF (0.25, 0.5, and 5 µg). In experiment 2, animals were tested for their locomotor response to ICV injections of 0.5 µg CRF after drug-free periods of 1–2, 10–11 and 28–29 days.

Results

Compared to saline pre-exposed animals, cocaine pre-exposed animals showed a significantly greater locomotor response to CRF, relative to vehicle, at all doses tested (experiment 1) and after drug-free periods of up to 28 days (experiment 2). The effects were clear and extremely consistent in magnitude between experiments and conditions.

Conclusions

These results suggest that cocaine pre-exposure induces long-term changes in the responsivity of the central nervous system to CRF.

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Acknowledgements

We thank Zhaoxia Li for her expert technical assistance in the running of these studies. This study was supported in part by grants from the Natural Sciences and Engineering Research Council of Canada to S.E. and the Ontario Mental Health Foundation and National Institute on Alcohol Abuse and Alcoholism to A.D.L.

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Authors and Affiliations

  1. Centre for the Neurobiology of Stress, Departments of Life Sciences and Psychology, University of Toronto at Scarborough, Scarborough, Ontario, Canada, M1A 1C4

    Suzanne Erb

  2. Biobehavioural Pharmacology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada

    Douglas Funk & Anh Dzung Lê

  3. Departments of Pharmacology and Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Anh Dzung Lê

Authors
  1. Suzanne Erb
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  2. Douglas Funk
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  3. Anh Dzung Lê
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Correspondence to Suzanne Erb.

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Erb, S., Funk, D. & Lê, A.D. Prior, repeated exposure to cocaine potentiates locomotor responsivity to central injections of corticotropin-releasing factor (CRF) in rats. Psychopharmacology 170, 383–389 (2003). https://doi.org/10.1007/s00213-003-1556-1

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  • DOI: https://doi.org/10.1007/s00213-003-1556-1

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