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The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immunoreactivity

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Abstract

The ability of kappa opioid agonists to modulate dopamine-mediated behavior and Fos immunore-activity was assessed in adult rats. It was predicted that kappa agonist treatment would block the unconditioned and conditioned behaviors produced by cocaine (an indirect dopamine agonist). In the initial experiments, cocaine-induced locomotor activity was assessed after either acute or chronic injections of the kappa receptor agonist U-50,488 (5 mg/kg, SC). As expected, U-50,488 decreased cocaine-induced activity, while leaving baseline activity levels unaffected. Interestingly, chronic treatment with U-50,488 did not induce behavioral tolerance. The conditioned effects of cocaine (20 mg/kg, IP) were assessed using the conditioned place preference (CPP) paradigm. As expected, rats showed a preference for the cocaine-paired compartment, an effect blocked by U-50,488 (5 mg/kg, SC). One hour after CPP testing, rats were killed and Fos immunoreactivity was assessed. Rats conditioned with cocaine, but not U-50,488, showed increased Fos activity in the anterior cingulate cortex, piriform cortex, lateral septal area, and olfactory tubercles. When considered together, these results suggest that U-50,488 was effective at blocking the unconditioned and conditioned effects of cocaine, as well as cocaine-induced neuronal activity (as measured by Fos induction).

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Author notes

  1. C. A. Crawford

    Present address: Mental Retardation Research Center, Neuropsychiatric Institute, University of California, 90024, Los Angeles, CA, USA

Authors and Affiliations

  1. Department of Psychiatry, University of California at San Francisco, and VA Medical Center, 94202, San Francisco, CA, USA

    C. A. Crawford, S. Hall & S. P. Berger

  2. Department of Psychology, California State University, 92407, San Bernardino, CA, USA

    S. A. McDougall & C. A. Bolanos

Authors
  1. C. A. Crawford
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  2. S. A. McDougall
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  3. C. A. Bolanos
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  4. S. Hall
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  5. S. P. Berger
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Crawford, C.A., McDougall, S.A., Bolanos, C.A. et al. The effects of the kappa agonist U-50,488 on cocaine-induced conditioned and unconditioned behaviors and Fos immunoreactivity. Psychopharmacology 120, 392–399 (1995). https://doi.org/10.1007/BF02245810

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  • DOI: https://doi.org/10.1007/BF02245810

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