Cannabinoid CB1 receptor activation mediates the opposing effects of amphetamine on impulsive action and impulsive choice.
| Title: | Cannabinoid CB1 receptor activation mediates the opposing effects of amphetamine on impulsive action and impulsive choice. |
|---|---|
| Authors: | Wiskerke J; Department of Anatomy and Neurosciences, VU University Medical Center, Amsterdam, The Netherlands.; Stoop N; Schetters D; Schoffelmeer AN; Pattij T |
| Source: | PloS one [PLoS One] 2011; Vol. 6 (10), pp. e25856. Date of Electronic Publication: 2011 Oct 07. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: San Francisco, CA : Public Library of Science |
| MeSH Terms: | Amphetamine/*pharmacology ; Choice Behavior/*drug effects ; Impulsive Behavior/*chemically induced ; Impulsive Behavior/*metabolism ; Receptor, Cannabinoid, CB1/*metabolism; Behavior, Animal/drug effects ; Dronabinol/analogs & derivatives ; Dronabinol/pharmacology ; Impulsive Behavior/psychology ; Piperidines/pharmacology ; Pyrans/pharmacology ; Pyrazoles/pharmacology ; Receptor, Cannabinoid, CB1/antagonists & inhibitors ; Animals ; Drug Inverse Agonism ; Rats ; Rats, Wistar ; Reward ; Rimonabant |
| Abstract: | It is well known that acute challenges with psychostimulants such as amphetamine affect impulsive behavior. We here studied the pharmacology underlying the effects of amphetamine in two rat models of impulsivity, the 5-choice serial reaction time task (5-CSRTT) and the delayed reward task (DRT), providing measures of inhibitory control, an aspect of impulsive action, and impulsive choice, respectively. We focused on the role of cannabinoid CB1 receptor activation in amphetamine-induced impulsivity as there is evidence that acute challenges with psychostimulants activate the endogenous cannabinoid system, and CB1 receptor activity modulates impulsivity in both rodents and humans. Results showed that pretreatment with either the CB1 receptor antagonist/inverse agonist SR141716A or the neutral CB1 receptor antagonist O-2050 dose-dependently improved baseline inhibitory control in the 5-CSRTT. Moreover, both compounds similarly attenuated amphetamine-induced inhibitory control deficits, suggesting that CB1 receptor activation by endogenously released cannabinoids mediates this aspect of impulsive action. Direct CB1 receptor activation by Δ9-Tetrahydrocannabinol (Δ9-THC) did, however, not affect inhibitory control. Although neither SR141716A nor O-2050 affected baseline impulsive choice in the DRT, both ligands completely prevented amphetamine-induced reductions in impulsive decision making, indicating that CB1 receptor activity may decrease this form of impulsivity. Indeed, acute Δ9-THC was found to reduce impulsive choice in a CB1 receptor-dependent way. Together, these results indicate an important, though complex role for cannabinoid CB1 receptor activity in the regulation of impulsive action and impulsive choice as well as the opposite effects amphetamine has on both forms of impulsive behavior. |
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| Substance Nomenclature: | 0 ((6aR,10aR)-3-(1-methansulfonylamino-4-hexyn-6-yl)6a,7,10,10a-tetrahydro-6,6,9-trimethyl-6H-dibenzo(b,d)pyran); 0 (Piperidines); 0 (Pyrans); 0 (Pyrazoles); 0 (Receptor, Cannabinoid, CB1); 7J8897W37S (Dronabinol); CK833KGX7E (Amphetamine); RML78EN3XE (Rimonabant) |
| Entry Date(s): | Date Created: 20111022 Date Completed: 20120213 Latest Revision: 20250915 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC3189229 |
| DOI: | 10.1371/journal.pone.0025856 |
| PMID: | 22016780 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't