title: Acute administration of Δ⁹ tetrahydrocannabinol does not prevent enhancement of sensory gating by clozapine in DBA/2 mice.
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.
authors.affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Research Service, Denver VA Medical Center, Denver, CO, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA. Electronic address: Jason.Smucny@ucdenver.edu.
authors.forename: Jason
authors.initials: J
authors.lastname: Smucny
authors.affiliation: Research Service, Denver VA Medical Center, Denver, CO, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Stevens
authors.affiliation: Neuroscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO, USA; Research Service, Denver VA Medical Center, Denver, CO, USA; Department of Psychiatry, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
authors.forename: Jason R
authors.initials: JR
authors.lastname: Tregellas
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000009:adverse effects; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000502:physiology; D003024:Clozapine / Q000008:administration & dosage* / Q000009:adverse effects*; D003213:Conditioning, Psychological; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000008:administration & dosage* / Q000009:adverse effects; D004347:Drug Interactions; D005072:Evoked Potentials, Auditory / Q000187:drug effects; D006801:Humans; D008297:Male; D002189:Marijuana Abuse / Q000150:complications / Q000503:physiopathology; D051379:Mice; D008811:Mice, Inbred DBA; D023421:Models, Animal; D011619:Psychotropic Drugs / Q000008:administration & dosage* / Q000009:adverse effects; D012559:Schizophrenia / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D055139:Sensory Gating / Q000187:drug effects* / Q000502:physiology
chemical_list: D014150:Antipsychotic Agents; D011619:Psychotropic Drugs; D013759:Dronabinol; D003024:Clozapine
keywords: Cannabinoid; Clozapine; DBA/2; Gating; P50; Schizophrenia