Psychology, Department of


Date of this Version



ACS Chem. Neurosci. (2010), 1, 265–278


Copyright 2010 American Chemical Society


The discovery that delta-9-tetrahydrocannabinol

9-THC) is the primary psychoactive ingredient in

marijuana prompted research that helped elucidate

the endogenous cannabinoid system of the brain.

Δ9-THC and other cannabinoid ligands with agonist

action (CP 55,940, HU210, and WIN 55,212-2)

increase firing of dopamine neurons and increase

synaptic dopamine in brain regions associated with

reward and drug addiction. Such changes in cellular

processes have prompted investigators to examine

the conditioned rewarding effects of the cannabinoid

ligands using the place conditioning task with rats and

mice. As reviewed here, these cannabinoid ligands

can condition place preferences (evidence for rewarding

effects) and place aversions (evidence for aversive

qualities). Notably, the procedural details used

in these place conditioning studies have varied across

laboratories. Such variation includes differences

in apparatus type, existence of procedural biases,

dose, number of conditioning trials, injectionto-

placement intervals, and pretraining drug exposure.

Some differences in outcome across studies can

be explained by these procedural variables. For

example, low doses of Δ9-THC appear to have conditioned

rewarding effects, whereas higher doses

have aversive effects that either mask these rewarding

effects or condition a place aversion. Throughout

this review, we highlight key areas that need further


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