Abstract
AIMS: Acute and chronic Δ(9)-THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ(9)-THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ(9)-THC's effects on CB1R and MOR levels and locomotor activity. MAIN METHODS: Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ(9)-THC [0.75mg/kg (low dose or LD) or 2.0 mg/kg (high dose or HD)] or vehicle for 24 days, and locomotion in the open field was tested after the first and fourth weeks of chronic Δ(9)-THC exposure. Brains were harvested at the end of treatment. [(3)H] SR141716A and [(3)H] DAMGO autoradiography assessed CB1R and MOR levels, respectively. KEY FINDINGS: Relative to each other, chronic HD rats showed reduced vertical plane (VP) entries and time, while LD rats had increased VP entries and time for locomotion, as assessed by open-field testing; no effects were found relative to the control. Autoradiography analyses showed that HD Δ(9)-THC significantly decreased CB1R binding relative to LD Δ(9)-THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ(9)-THC rats displayed elevated binding in the primary motor (33% increase) and hypothalamic (33% increase) regions compared with controls. No significant differences were observed in MOR binding for the LD or HD compared to the control. SIGNIFICANCE: These results demonstrate that chronic Δ(9)-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.