Systemic, but not local, administration of cannabinoid CB1 receptor agonists modulate prefrontal cortical acetylcholine efflux in the rat

Drugs acting on brain cannabinoid CB1 receptors exert complex actions on modulatory transmitters that are involved in attention and cognition; however, little is known about the precise pharmacological and anatomical mechanisms that govern these effects. Previously demonstrated effects of cannabinoids on acetylcholine (ACh) in the hippocampus prompted us to evaluate changes in the prefrontal cortex, a site associated with mnemonic and attentional functions. We utilized in vivo microdialysis, coupled with direct reverse perfusion of agents, to study the actions on cannabinoidergic drugs on ACh release within the rat frontal cortex. Systemic administration of the CB1 receptor agonists Δ9‐tetrahydrocannabinol (THC) or WIN 55,212‐2 (WIN) dose‐ and time‐dependently increased ACh release; these effects were blocked by pretreatment with the selective CB1 receptor antagonist / partial inverse agonist SR141716A (SR). THC applied by reverse dialysis in the frontal cortex caused no change in ACh release, although intrastriatal infusions of THC decreased ACh efflux. These data indicate that cannabinoid agonists potentiate ACh release in the frontal cortex by activating cannabinoid receptors in brain regions other than the frontal cortex. Synapse 48:178–183, 2003. © 2003 Wiley‐Liss, Inc.