RT Journal Article
SR Electronic
T1 CHRONIC Δ9-THC IN RHESUS MONKEYS: EFFECTS ON COGNITIVE PERFORMANCE AND DOPAMINE D2/D3 RECEPTOR AVAILABILITY
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP jpet.117.244194
DO 10.1124/jpet.117.244194
A1 William S John
A1 Thomas J Martin
A1 Kiran K Solingapuram Sai
A1 Susan H Nader
A1 H D Gage
A1 Akiva Mintz
A1 Michael A Nader
YR 2017
UL http://jpet.aspetjournals.org/content/early/2017/12/04/jpet.117.244194.abstract
AB Cannabis-related impairments to cognitive function may represent novel therapeutic targets for cannabis-use disorder, although the nature, persistence, and reversibility of those deficits remain unclear. Adult male rhesus monkeys (N=6) responded in the mornings on tasks designed to assess different cognitive domains using CANTAB touchscreens followed by responding maintained under a fixed-ratio (FR) 10 schedule of food presentation in different operant chambers. First, the acute effects of Δ9-tetrahydrocannabinol (THC; 0.01-0.56 mg/kg, i.v.) on cognitive performance, FR responding and body temperature were determined. Next, THC (1.0-2.0 mg/kg, s.c.) was administered daily after FR10 sessions for 12 weeks during which the residual effects of THC (i.e., 22 hrs after administration) on cognition were examined and the acute effects of THC were redetermined. In a subgroup of monkeys, dopamine D2/D3 receptor availability was assessed after 4 weeks of chronic THC exposure and compared to drug-naive controls using positron emission tomography and [11C]-raclopride (N=4/group). Acute THC pretreatments dose-dependently decreased FR responding and body temperature, while impairment to cognitive performance was task specific. During chronic treatment, THC produced persistent residual impairment only to working memory; tolerance differentially developed to acute cognitive impairments. There was recovery from residual cognitive impairments to working memory within 2 weeks of abstinence. Compared to controls, D2/D3 receptor availability was not altered during chronic THC treatment. In conclusion, THC-induced disruptions in cognition were task-specific, as was tolerance development, and not related to changes in D2/D3 receptor availability. Intervention strategies for cannabis-use disorder that enhance working memory performance may facilitate positive treatment outcomes.