title: Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex.
abstract: Marijuana (Cannabis sativa) is one of the most widely used illicit drugs in the world. Its use is associated with impairments in cognitive function. We previously reported that Δ(9)-tetrahydrocannabinol (Δ(9)-THC), the primary psychoactive component of marijuana, impaired spatial working memory in the radial maze task when injected intracortically (IC) into the medial prefrontal cortex (mPFC) of rats. Here, we used this paradigm to evaluate the involvement of prefrontal dopamine receptors in working memory disruption induced by Δ(9)-THC. Intracortical pre-treatment of animals with either the D(1)- or D(2)-like dopamine receptor antagonists SCH 23390 or clozapine, respectively, significantly reduced the number of errors rats made in the radial maze following treatment with Δ(9)-THC also administered intracortically. These results were obtained in the absence of locomotor impairment, as evidenced by the time spent in each arm a rat visited. Our findings suggest that prefrontal dopamine receptors are involved in Δ(9)-THC-induced disruption of spatial working memory. This interaction between the cannabinoid system and dopamine release in the PFC contributes to new directions in research and to treatments for cognitive dysfunctions associated with drug abuse and dependence.
authors.affiliation: Federal University of Espirito Santo, Vitória, ES, Brazil. susuvi@terra.com.br
authors.forename: Lívia Carla de Melo
authors.initials: LC
authors.lastname: Rodrigues
authors.forename: Catarine Lima
authors.initials: CL
authors.lastname: Conti
authors.forename: Ester Miyuki
authors.initials: EM
authors.lastname: Nakamura-Palacios
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000494:pharmacology* / Q000627:therapeutic use; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D013759:Dronabinol / Q000037:antagonists & inhibitors*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy* / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D011619:Psychotropic Drugs / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D011619:Psychotropic Drugs; C534628:SCH 23390; D013759:Dronabinol; D003024:Clozapine