AIMS

Acute and chronic Δ-THC exposure paradigms affect the body differently. More must be known about the impact of chronic Δ-THC on cannabinoid-1 (CB1R) and mu-opioid (MOR) receptor levels in the brain. The present study examined chronic Δ-THC's effects on CB1R and MOR levels and locomotor activity.

MAIN METHODS

Adolescent Sprague-Dawley rats were given daily intraperitoneal injections of Δ-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-THC exposure. Brains were harvested at the end of treatment. [H] SR141716A and [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-THC significantly decreased CB1R binding relative to LD Δ-THC in the cingulate (33%), primary motor (42%), secondary motor (33%) somatosensory (38%), rhinal (38%), and auditory (50%) cortices; LD Δ-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-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.