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Effect of footshock stress on place conditioning produced by Δ9-tetrahydrocannabinol and the fatty acid amide hydrolase (FAAH) inhibitor, URB597, in Sprague-Dawley rats

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Abstract

Rationale

Unlike other drugs of abuse, Δ9-tetrahydrocanabinol (THC) is generally aversive in rodent conditioned place preference models, but little is known about how stress may modify THC affective properties.

Objective

We evaluate the potential of footshock stress to enhance the rewarding effects of THC and the fatty acid amide hydrolase inhibitor, URB597, as it has been shown to enhance their anxiolytic effects.

Materials and methods

The effect of footshock stress 24 h prior to each conditioning trial on the rewarding/aversive effects of THC (1, 0.1, 0.5 mg/kg, ip) and URB597 (0.3 mg/kg, ip) was evaluated in an unbiased place conditioning procedure in rats. Subsequently, the same stressor was given immediately prior to conditioning with THC (1 and 0.1 mg/kg). Locomotor activity was also measured during conditioning.

Results

A dose of 1 mg/kg THC, but not 0.1–0.5 mg/kg, produced a conditioned place aversion (CPA) that was not modified by footshock delivered 24 h prior to conditioning trials; however, footshock delivered immediately prior to conditioning trials prevented that CPA. Lower doses of THC and URB597 produced no place conditioning regardless of footshock conditions. A dose of 1 mg/kg THC produced locomotor suppression during conditioning trials that was prevented by footshock delivered 24 h before and reversed to locomotor activation by footshock delivered immediately before conditioning.

Conclusions

Unlike the effect of footshock on THC- and URB597-induced anxiolytic effects, footshock does not promote THC or URB597-induced reward in a conditioned place preference paradigm. However, footshock stress reverses the sedative effects of 1 mg/kg THC.

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Acknowledgments

The idea for the stress manipulation arose from a question asked by Dr. Aron Lichtman during the International Cannabinoid Research Society Meetings, Bukovina, Poland, 2016. This research was supported by grants from the Natural Science and Engineering Research Council (92057) and the Canadian Institutes or Health Reaserch (137122) to L. Parker.

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Authors and Affiliations

  1. Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, N1G 2W1, Canada

    Marieka V. DeVuono, Kiri L. Wills, Danielle V. MacPherson, Kelly M. Hrelja & Linda A. Parker

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  1. Marieka V. DeVuono
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  2. Kiri L. Wills
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  3. Danielle V. MacPherson
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  4. Kelly M. Hrelja
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  5. Linda A. Parker
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Correspondence to Linda A. Parker.

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All animal procedures were approved by the Animal Care Committee of the University of Guelph and adhere to the guidelines of the Canadian Council of Animal Care.

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DeVuono, M.V., Wills, K.L., MacPherson, D.V. et al. Effect of footshock stress on place conditioning produced by Δ9-tetrahydrocannabinol and the fatty acid amide hydrolase (FAAH) inhibitor, URB597, in Sprague-Dawley rats. Psychopharmacology 234, 3229–3240 (2017). https://doi.org/10.1007/s00213-017-4714-6

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