Persistent effects of chronic Δ9-THC exposure on motor impulsivity in rats.
BACKGROUND
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.
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-2001, 10550 N. Torrey Pines Road, La Jolla, CA, 92037, USA.
Cristina
C
Irimia
Ilham Y
IY
Polis
David
D
Stouffer
Loren H
LH
Parsons
D000818:Animals; D001288:Attention / Q000187:drug effects*; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D007175:Impulsive Behavior / Q000187:drug effects*; D007266:Inhibition, Psychological; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
D063386:Cannabinoid Receptor Agonists; D013759:Dronabinol