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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.

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  • Authors+Show Affiliations

    ,

    Federal University of Espirito Santo, Vitória, ES, Brazil. susuvi@terra.com.br

    ,

    Source

    Brain research 1382: 2011 Mar 25 pg 230-7

    MeSH

    Animals
    Benzazepines
    Clozapine
    Disease Models, Animal
    Dopamine Antagonists
    Dronabinol
    Male
    Maze Learning
    Memory Disorders
    Prefrontal Cortex
    Psychotropic Drugs
    Rats
    Rats, Wistar

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural

    Language

    eng

    PubMed ID

    21281616

    Citation

    Rodrigues, Lívia Carla de Melo, et al. "Clozapine and SCH 23390 Prevent the Spatial Working Memory Disruption Induced By Δ9-THC Administration Into the Medial Prefrontal Cortex." Brain Research, vol. 1382, 2011, pp. 230-7.
    Rodrigues LC, Conti CL, Nakamura-Palacios EM. Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex. Brain Res. 2011;1382:230-7.
    Rodrigues, L. C., Conti, C. L., & Nakamura-Palacios, E. M. (2011). Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex. Brain Research, 1382, pp. 230-7. doi:10.1016/j.brainres.2011.01.069.
    Rodrigues LC, Conti CL, Nakamura-Palacios EM. Clozapine and SCH 23390 Prevent the Spatial Working Memory Disruption Induced By Δ9-THC Administration Into the Medial Prefrontal Cortex. Brain Res. 2011 Mar 25;1382:230-7. PubMed PMID: 21281616.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Clozapine and SCH 23390 prevent the spatial working memory disruption induced by Δ9-THC administration into the medial prefrontal cortex. AU - Rodrigues,Lívia Carla de Melo, AU - Conti,Catarine Lima, AU - Nakamura-Palacios,Ester Miyuki, Y1 - 2011/01/28/ PY - 2010/10/11/received PY - 2011/01/18/revised PY - 2011/01/20/accepted PY - 2011/2/2/entrez PY - 2011/2/2/pubmed PY - 2011/11/16/medline SP - 230 EP - 7 JF - Brain research JO - Brain Res. VL - 1382 N2 - 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. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/21281616/abstract/Clozapine_and_SCH_23390_prevent_the_spatial_working_memory_disruption_induced_by_Δ9_THC_administration_into_the_medial_prefrontal_cortex_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(11)00153-3 DB - PRIME DP - Unbound Medicine ER -