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

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.

Keywords: Fatty acid amide hydrolase (FAAH); Fear conditioning; Place conditioning; Stress; Δ9-tetrahydrocanabinol (THC).