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

Chronic exposure to Δ9-tetrahydrocannabinol (THC) in adolescent rats alters cannabinoid-1 receptor (CB1R) levels in the brain and affects locomotion in a dose-dependent manner. High-dose THC (2.0 mg/kg daily for 24 days) reduced vertical activity in an open field and decreased CB1R binding in several cortical regions (cingulate, motor, somatosensory, rhinal, and auditory cortices) by 33–50% relative to low-dose THC. Low-dose THC (0.75 mg/kg) increased vertical activity and elevated CB1R binding in the primary motor cortex and hypothalamus by 33% compared to controls. No changes were found in mu-opioid receptor binding. The results indicate that chronic THC dose-dependently affects CB1R levels and motor behavior.

Study at a glance

Abstract

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. 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. 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. These results demonstrate that chronic Δ9-THC dose-dependently altered CB1R levels throughout the brain and locomotor activity in the open field.