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Δ9-THC administered into the medial prefrontal cortex disrupts the spatial working memory

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Abstract

Rationale

Δ9-Tetrahydrocannabinol (Δ9-THC) disrupts working memory. The prefrontal cortex (PFC) is involved in the processing of working memory, and its medial portion (mPFC) is part of a brain reward circuit as constituted by the mesocorticolimbic dopaminergic system.

Objective

This study examined the involvement of the mPFC in the effects of Δ9-THC on spatial working memory.

Methods

Ten male Wistar rats well-trained in a radial arm maze and with bilateral cannula implanted in the mPFC received Δ9-THC intracortically (Δ9-THC IC) at doses of 0 (VEH), 32, 100 or 180 μg, 5 min before a 5-s or a 1-h delayed task in order to measure a short- or long-term spatial working memory, respectively. By contrast, 11 other animals received Δ9-THC intraperitoneally (Δ9-THC IP) at doses of 0 (VEH), 0.32, 1 or 1.8 mg/kg, 30 min before a 5-s or a 1-h delayed task. Additionally, after a 15-day washout, the effect of an IP or IC pre-exposure of Δ9-THC was examined by repeating both dose–effect curves in a crossover order for the routes of administration.

Results

Δ9-THC IP produced significantly larger number of errors at doses of 0.32 or 1 mg/kg as compared to VEH in the 1-h post-delay performance. Δ9-THC 100 μg IC also produced significantly larger number of errors as compared to VEH and also to the other doses (32 or 180 μg) IC in the 1-h post-delay performance. Previous exposure to Δ9-THC IP or IC did not significantly affect the disruptive effect of this cannabinoid.

Conclusions

Δ9-THC administered directly in the mPFC impaired 1-h delayed task in the radial arm maze in a manner similar to that observed for its systemic administration, suggesting that the mPFC is involved in the disruptive effects of Δ9-THC on spatial working memory.

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Acknowledgements

We thank CAPES and CNPq for student fellowships to AP Cruz, LCS Melo, AR Marinho, and SJR Valentim Jr. We are also grateful to Louis Allen Barker, Ph.D., Emeritus Professor of Pharmacology, Louisiana State University Health Sciences Center (New Orleans, LA) for his critical comments and suggestions on this manuscript, and also for revising the English language. The cannabinoid used in this study was provided through the courtesy of the National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH).

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Authors and Affiliations

  1. Department of Physiological Sciences, Federal University of Espírito Santo, Av. Marechal Campos, 1468, B. Maruípe, 29042-755, Vitória, ES, Brazil

    Lívia Carla Silva de Melo, Ariane Pinheiro Cruz, Saavedra José Rios Valentim Jr, Andresa Rosane Marinho, Josidéia Barreto Mendonça & Ester Miyuki Nakamura-Palacios

  2. Programa de Pós-Graduação em Ciências Fisiológicas, Centro Biomédico, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, 29042-755, Vitória, ES, Brazil

    Ester Miyuki Nakamura-Palacios

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  1. Lívia Carla Silva de Melo
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  2. Ariane Pinheiro Cruz
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  3. Saavedra José Rios Valentim Jr
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Correspondence to Ester Miyuki Nakamura-Palacios.

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de Melo, L.C.S., Cruz, A.P., Valentim, S.J.R. et al. Δ9-THC administered into the medial prefrontal cortex disrupts the spatial working memory. Psychopharmacology 183, 54–64 (2005). https://doi.org/10.1007/s00213-005-0141-1

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