Acute administration of Δ⁹ tetrahydrocannabinol does not prevent enhancement of sensory gating by clozapine in DBA2 mice.
Despite high rates of marijuana abuse in schizophrenia, the physiological interactions between tetrahydrocannabinol (THC) and antipsychotic medications are poorly understood. A well-characterized feature of schizophrenia is poor gating of the P50 auditory-evoked potential. This feature has been translationally modeled by the DBA2 mouse, which exhibits poor suppression of the P20-N40 AEP, the rodent analog of the human P50. Previous work has demonstrated that this deficit is reversed by the antipsychotic clozapine. It is unknown, however, if this effect is altered by THC administration. Using a conditioning-testing paradigm with paired auditory stimuli, the effects of clozapine and dronabinol (a pharmaceutical THC formulation) on inhibitory P20-N40 AEP processing were assessed from in vivo hippocampal CA3 recordings in anesthetized DBA2 mice. The effects of clozapine (0.33 mgkg) and dronabinol (10 mgkg) were assessed alone and in combination (0.33, 1 or 1.83 mgkg clozapine with 10mgkg dronabinol). Improved P20-N40 AEP gating was observed after acute administration of 0.33 mgkg clozapine. Co-injection of 0.33 mgkg clozapine and 10 mgkg THC, however, did not improve gating relative to baseline. This effect was overcome by higher doses of clozapine (1 and 1.83 mgkg), as these doses improved gating relative to baseline in the presence of 10 mgkg THC. 10 mgkg THC alone did not affect gating. In conclusion, THC does not prevent improvement of P20-N40 gating by clozapine.