Stress-induced sensitization of cortical adrenergic receptors following a history of cannabinoid exposure

► WIN 55,212-2 pre-treatment decreases stress-induced norepinephrine release in frontal cortex. ► Acute WIN 55,212-2 exposure desensitizes cortical α2-adrenergic receptors (α2-AR). ► Cannabinoid modulation of adrenergic receptors is stress-dependent. ► Stress prevented the desensitization of α2-ARs produced by a history of cannabinoid exposure.