Local administration of a cannabinoid agonist alters norepinephrine efflux in the rat frontal cortex.
M E Page, V C Oropeza, E J Van Bockstaele
Neuroscience Letters January 24, 2008 DOI: 10.1016/j.neulet.2007.11.009 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adult male Sprague-Dawley rats |
| Interventions | WIN 55 212-2 SR 141716A |
| Dose | WIN 55,212-2 15 mg/kg i.p.; WIN 55,212-2 100 microM; SR 141716A 300 microM |
| Key findings | Local blockade of cortical CB1 receptors with SR 141716A attenuated the increase in frontal cortex norepinephrine efflux produced by systemic WIN 55,212-2, and direct cortical perfusion of WIN 55,212-2 itself increased norepinephrine efflux. Unexpectedly, local SR 141716A followed by local WIN 55,212-2 inhibited norepinephrine efflux, which the authors describe as paradoxical. |
Abstract
Delta(9)-tetrahydrocannabinol, the main psychoactive ingredient in marijuana, activates specific cannabinoid (CB) receptors to exert complex actions on modulatory neurotransmitters involved in attention and cognition. Previous research has demonstrated that systemic administration of the synthetic cannabinoid agonist, WIN 55,212-2, increases norepinephrine efflux in the frontal cortex. The distribution of CB1 receptors on noradrenergic fibers in the frontal cortex suggests this may be one potential site for the regulation of norepinephrine release. In the present study, we first examined the ability of a CB1 antagonist, applied locally in the frontal cortex of adult male Sprague-Dawley rats, to block the actions of systemic WIN 55,212-2. Pretreatment with SR 141716A (300 microM) significantly attenuated the excitatory effects of WIN 55,212-2 (15 mg/kg, i.p.). Next, the impact of direct perfusion of WIN 55,212-2 into the frontal cortex on extracellular norepinephrine efflux was measured. Direct application of WIN 55,212-2 (100 microM) into the frontal cortex elicited a significant increase in extracellular norepinephrine efflux suggesting that activation of cortical cannabinoid receptors contributes to alterations in norepinephrine levels in this brain region. Finally, local administration of SR 141716A followed by local administration of WIN 55,212-2 revealed a paradoxical inhibition of norepinephrine efflux.