Δ9-Tetrahydrocannabinol Increases Prefrontal Cortical Catecholaminergic Utilization and Impairs Spatial Working Memory in the Rat: Blockade of Dopaminergic Effects with HA966 (original) (raw)
- Original Article
- Published: 01 June 1997
- Ericka Andrusiak BS2,
- Anh Tran BA2,
- Malcolm B Bowers Jr MD3 &
- …
- Robert H Roth Ph.D2,3
Neuropsychopharmacology volume 16, pages 426–432 (1997)Cite this article
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Abstract
The present study examined Δ9-tetrahydrocannabinol (THC)-induced alterations in monoamine transmission in the rat forebrain as well as the effects of the enantiomers of 3-amino-1-hydroxypyrrolid-2-one (HA966) on the monoamine response to THC. Activation of dopamine (DA) and norepinephrine (NE) but not serotonin (5-HT) turnover in the prefrontal cortex (PFC) was observed after THC (5 mg/kg i.p.) administration. Both enantiomers of HA966 completely prevented the effects of THC on PFC DA turnover and partially blocked the THC-induced rise in NE metabolism. The cognitive consequences of THC exposure were also examined. THC significantly impaired spatial working, but not reference, memory in rats, and this effect was ameliorated by HA966. Thus, HA966 prevents the THC-induced increases in PFC DA turnover and impairments of prefrontal cortical working memory function. Furthermore, these data suggest that cognitive impairments displayed by marijuana self-administering humans may be related to PFC DA hyperactivity and that HA966 may prevent this effect.
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Authors and Affiliations
- From the Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut
J David Jentsch BA - Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut
Ericka Andrusiak BS, Anh Tran BA & Robert H Roth Ph.D - Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
Malcolm B Bowers Jr MD & Robert H Roth Ph.D
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- J David Jentsch BA
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Jentsch, J., Andrusiak, E., Tran, A. et al. Δ9-Tetrahydrocannabinol Increases Prefrontal Cortical Catecholaminergic Utilization and Impairs Spatial Working Memory in the Rat: Blockade of Dopaminergic Effects with HA966.Neuropsychopharmacol 16, 426–432 (1997). https://doi.org/10.1016/S0893-133X(97)00018-3
- Received: 09 July 1996
- Accepted: 21 October 1996
- Published: 01 June 1997
- Issue Date: 01 June 1997
- DOI: https://doi.org/10.1016/S0893-133X(97)00018-3