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Effects of endocannabinoid neurotransmission modulators on brain stimulation reward

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Abstract

Rationale

The endogenous cannabinoid system is responsive to the neurobiological actions of Δ9-tetrahydrocannabinol (THC) and other cannabinoid ligands. While numerous studies have focused on the behavioral and pharmacological effects of THC and cannabinoid agonists in experimental animals, most recent work focuses on compounds that modulate endocannabinoid neurotransmission. However, the relevant studies concerning the ability of endocannabinoid modulators to modify reward processes in experimental animals remain rather scarce.

Objectives

The present study examined the effects of drugs modulating endocannabinoid neurotransmission on brain reward function using the rate–frequency curve shift paradigm of intracranial self-stimulation (ICSS).

Methods

Animals were implanted with electrodes into the medial forebrain bundle (MFB). After brain stimulation reward thresholds stabilized, rats received intraperitoneal injections of the fatty acid amide hydrolase (FAAH) inhibitors phenylmethylsulfonyl fluoride (PMSF) (0, 15, 30, and 60 mg/kg) and URB-597 (0, 0.3, 1, and 3 mg/kg) and the selective anandamide reuptake inhibitor OMDM-2 (0, 3, 10, and 30 mg/kg).

Results

The highest dose of URB-597 and OMDM-2 significantly increased the threshold frequency required for MFB ICSS, while PMSF increased the threshold frequency in all doses tested. The cannabinoid 1 (CB1) receptor antagonist SR141716A reversed the actions of URB-597 and OMDM-2, but not PMSF, without affecting reward thresholds by itself.

Conclusions

These results indicate that under the present experimental conditions endocannabinoid modulators do not exhibit reinforcing properties, but rather have inhibitory influence on reward processes. The anhedonic effects of URB-597 and OMDM-2, but not PMSF, observed at the highest doses in this study are probably mediated through direct CB1 receptor stimulation.

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Acknowledgements

This study was supported by a grant from the Research Committee (KA 2303) and the Department of Psychology of the University of Crete. Styliani Vlachou was supported by a scholarship from PROPONTIS Foundation.

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Authors and Affiliations

  1. Laboratory of Behavioral Neuroscience, Department of Psychology, School of Social Sciences, University of Crete, 74100 Rethymnon, Crete, Greece

    Styliani Vlachou & George Panagis

  2. Neuroscience Research, Lilly Corporate Center, Eli Lilly and Company, Indianapolis, IN, 46285-0510, USA

    George G. Nomikos

Authors
  1. Styliani Vlachou
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  2. George G. Nomikos
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  3. George Panagis
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Correspondence to George Panagis.

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Vlachou, S., Nomikos, G.G. & Panagis, G. Effects of endocannabinoid neurotransmission modulators on brain stimulation reward. Psychopharmacology 188, 293–305 (2006). https://doi.org/10.1007/s00213-006-0506-0

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  • DOI: https://doi.org/10.1007/s00213-006-0506-0

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