Dopamine, γ-aminobutyric acid, and glutamate balance in the nucleus accumbens shell: Differential effects of cannabinoid 1 receptor agonists Δ9-Tetrahydrocannabinol, AM11101, and AM8936.
Neuropharmacology June 1, 2026 Evan C Smith, Christos Iliopoulos-Tsoutsouvas, Markos-Orestis Georgiadis et al.
The neurochemical effects of cannabinoids in reward-related brain regions are not fully understood. Using microdialysis in male mice, single injections of delta-9-tetrahydrocannabinol (Δ9-THC) and synthetic CB1 agonists (partial AM11101, full AM8936) altered dopamine, glutamate, and GABA balance in the nucleus accumbens shell over 5 hours. Low Δ9-THC doses increased dopamine and GABA; AM8936 increased all three neurotransmitters. High doses of Δ9-THC and AM8936 decreased dopamine, while only high AM8936 doses decreased GABA. AM11101 did not substantially alter neurotransmitters. Δ9-THC and AM8936, but not AM11101, increased conditioned place preference scores, indicating reward. The lack of neurochemical or behavioral effects of AM11101 suggests it may be a promising CB1-based pharmacotherapeutic.