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Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats

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Abstract

Rationale

In humans, long-term marijuana use is associated with impaired impulse control and attentional capacity, though it has been difficult to distinguish pre-existing cognitive deficits from possible consequences of prolonged marijuana exposure.

Objective

To evaluate the effects of long-term exposure to Δ9-Tetrahydrocannabinol (Δ9-THC), the primary psychoactive constituent in marijuana, on indices of impulse control and attentional capacity using the rat 5-Choice Serial Reaction Time Task (5-CSRTT).

Methods

Ten 14-day cycles of Δ9-THC dosing and 5-CSRTT testing were employed, each comprised of 5-day Δ9-THC dosing (0.3 or 3 mg/kg b.i.d.) and 5-CSRTT testing during the 9 days of drug abstinence. Subsequent 5-CSRTT testing continued during 5 weeks of protracted abstinence.

Results

Dose-dependent increases in motor impulsivity (premature responses) and behavioral disinhibition (perseverative responses) emerged following 5 cycles of Δ9-THC exposure that persisted for the remaining dosing and testing cycles. Δ9-THC-related disruptions in motor impulsivity and behavioral inhibition were most pronounced during cognitively challenging 5-CSRTT sessions incorporating varying novel inter-trial intervals (ITIs), and these disruptions persisted for at least 5 weeks of Δ9-THC abstinence. Δ9-THC-related impairments in attentional capacity (response accuracy) were also evident during variable ITI challenge tests, though these attentional disruptions abated within 3 weeks of Δ9-THC abstinence.

Conclusions

These observations demonstrate that long-term intermittent exposure to clinically meaningful Δ9-THC doses induces persistent impairments in impulse control and attentional function. If present in humans, these disruptions may impact academic and professional performance.

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Acknowledgments

This work was supported by NIDA grant P20 DA024194 and NIAAA grant RO1 AA022249-01S1. This is manuscript number 28056 from The Scripps Research Institute. The authors have no competing financial interest to declare.

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  1. Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2001, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA

    Cristina Irimia, Ilham Y. Polis, David Stouffer & Loren H. Parsons

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  1. Cristina Irimia
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  2. Ilham Y. Polis
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  4. Loren H. Parsons
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Correspondence to Loren H. Parsons.

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Irimia, C., Polis, I.Y., Stouffer, D. et al. Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats. Psychopharmacology 232, 3033–3043 (2015). https://doi.org/10.1007/s00213-015-3942-x

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  • DOI: https://doi.org/10.1007/s00213-015-3942-x

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