Delta 9–tetrahydrocannabinol ( ⁹-THC) is the primary psychoactive compound of Cannabis sativa, one of the oldest drugs of abuse. While the human abuse properties of⁹-THC are established, knowledge of its reinforcing and dependence-producing effects is limited. The rewarding properties of⁹-THC using rodent models are controversial (Valjent et at., 2000). Results obtained with conditioned place preference (CPP) are varied due to the frequency of false positives and variations in methodological details (Tanda et al., 2003). Cannabinoid agonists either suppress or induce place preference depending on factors, such as dose, timing of administration, and modifications of protocol procedures (Sanudo-Pena et al., 1997; Cheer et al., 2000). The objective of the study was to determine whether acute or chronic treatment with⁹-THC produced CPP in the rat, and to determine whether the behavioural effects after chronic treatment were associated with changes in dopamine turnover. All treatments were given intraperitoneally to male Lister hooded rats (250 – 300 g; n8) using an unbiased design. The CPP protocol used a two compartment box with neutral flooring texture and two distinct wall patterns in each compartment (Cheer et al., 2000). Immediately after the final period of CPP the rats treated chronically were killed and DA and DOPAC measured in the striatum using HPLC with electrochemical detection. For the acute studies, rats were exposed to three pairings of⁹-THC (3.0, 1.0, 0.5 & 0.1 mg/kg), cocaine (20 mg/kg) or vehicle (cremophor/ethanol/saline, 1:1:18) prior to exposure to the box on the last day without injection. For the chronic studies, rats were injected with⁹-THC (0.5 & 2.0 mg/kg) or vehicle every 48 hours for 21 days and exposed to the CPP box on the three final days of injection and 48 hours after the last injection. CPP data were analysed using Student t test and the neurochemical data by one way ANOVA with Dunnett test.

Cocaine (20 mg/kg) induced significant place preference (P <0.05) indicating that the method was effective in detecting reward, while vehicle treatment had no effect. Acute treatment with⁹-THC (3.0 mg/kg) induced significant place aversion (P <0.05), whereas lower doses (1.0, 0.1 & 0.5 mg/kg) had no significant effect on CPP. Chronic treatment with⁹-THC (0.5 & 2.0 mg/kg) had no significant effect on CPP. Striatal dopamine was significantly increased after chronic treatment with a greater increase after 0.5 mg/kg than after 2.0 mg/kg. There was a significant decrease in dopamine turnover (DOPAC:DA ratio) after both chronic treatments compared to vehicle treated controls. The results confirm findings showing that acute⁹-THC can induce aversion while chronic treatment had no effect on CPP but decreased dopamine turnover indicating that factors other than dopamine maybe involved in the behavioural effects of cannabinoids.

Cheer et al., 2000. Psychopharmacology 151: 25-30.
Sanudo-Pena et al., 1997. Neurosci Lett 223:125-128.
Tanda et al., 2003. Psychopharmacology 169:115-134.
Valjent et al., 2000. Psychopharmacology 147:436-438.