Chronic Δ9-tetrahydrocannabinol treatment has dose-dependent effects on open field exploratory behavior and [³H] SR141716A receptor binding in the rat brain

Aims: Acute and chronic Δ9-THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ9-THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ9-THC's effects on CB1R and MOR levels and locomotor activity. Main methods: Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ9-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 Δ9-THC exposure. Brains were harvested at the end of treatment. [3H] SR141716A and [3H] 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 Δ9-THC significantly decreased CB1R binding relative to LD Δ9-THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ9-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 Δ9-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.