Acute administration of Δ⁹ tetrahydrocannabinol does not prevent enhancement of sensory gating by clozapine in DBA/2 mice.
Jason Smucny, Karen E Stevens, Jason R Tregellas
Pharmacology, Biochemistry, and Behavior March 2014 DOI: 10.1016/j.pbb.2014.01.001 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | Anesthetized DBA/2 mice, an inbred strain used as a model of poor P50 auditory gating |
| Interventions | Clozapine Dronabinol |
| Dose | clozapine 0.33 mg/kg; dronabinol 10 mg/kg; combinations of 0.33, 1, or 1.83 mg/kg clozapine with 10 mg/kg dronabinol |
| Measures | P20-N40 auditory-evoked potential (AEP) gating, measured using a conditioning-testing paradigm with paired auditory stimuli |
| Topics | Cannabis |
| Keywords | Cannabinoid Clozapine Dba/2 Gating P50 Schizophrenia |
| Key findings | Acute clozapine at 0.33 mg/kg improved P20-N40 auditory-evoked potential gating in DBA/2 mice, but co-administration with 10 mg/kg dronabinol (THC) prevented this improvement at that dose. Higher clozapine doses (1 and 1.83 mg/kg) improved gating even with THC present, and THC alone did not affect gating. The authors conclude that THC does not prevent clozapine's gating improvement. |
Abstract
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 DBA/2 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 DBA/2 mice. The effects of clozapine (0.33 mg/kg) and dronabinol (10 mg/kg) were assessed alone and in combination (0.33, 1 or 1.83 mg/kg clozapine with 10mg/kg dronabinol). Improved P20-N40 AEP gating was observed after acute administration of 0.33 mg/kg clozapine. Co-injection of 0.33 mg/kg clozapine and 10 mg/kg THC, however, did not improve gating relative to baseline. This effect was overcome by higher doses of clozapine (1 and 1.83 mg/kg), as these doses improved gating relative to baseline in the presence of 10 mg/kg THC. 10 mg/kg THC alone did not affect gating. In conclusion, THC does not prevent improvement of P20-N40 gating by clozapine.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 2
Cites 3
- Effects of cannabis use on outcomes of psychotic disorders: systematic review The British Journal of Psychiatry October 31, 2008
- The Impact of Cannabis Use on Cognitive Functioning in Patients With Schizophrenia: A Meta-analysis of Existing Findings and New Data in a First-Episode Sample Schizophrenia Bulletin July 25, 2010
- Reversible and regionally selective downregulation of brain cannabinoid CB1 receptors in chronic daily cannabis smokers Molecular Psychiatry July 12, 2011