@entity9394 ( @entity14512 ) is the most potent endogenous ligand of brain cannabinoid @entity13677 receptors and is synthesized on demand from 2-arachidonate-containing @entity4357 by the action of @entity2366 lipase in response to increased intracellular @entity460 . Several studies indicate that the endocannabinoid (eCB) system is involved in the mechanism of reward and that diverse drugs of abuse increase brain eCB levels. In addition, eCB are self-administered (SA) by squirrel monkeys, and @entity9393 increases nucleus accumbens (NAc) shell @entity935 (DA) in @entity35 . To date, there is no evidence on the reinforcing effects of @entity14512 and its effects on DA transmission in rodents. In order to fill this gap, we studied intravenous @entity14512 SA and monitored the effect of @entity14512 on extracellular DA in the NAc shell and core via microdialysis in male @entity35 . @entity35 were implanted with jugular catheters and trained to self-administer @entity14512 [25   mg/kg/inf intravenously (iv)] in single daily 1   h sessions for 5   weeks under initial fixed ratio (FR) 1 schedule. The ratio was subsequently increased to FR2. Active nose poking increased from the 6th SA session (acquisition phase) but no significant increase of nose pokes was observed after FR2. When @entity14512 was substituted for vehicle (25th SA session, extinction phase), rate responding as well as number of injections slowly decreased. When vehicle was replaced with @entity14512 , SA behavior immediately recovered (reacquisition phase). The reinforcing effects of @entity14512 in SA behavior were fully blocked by the @entity13677 receptor inverse agonist/antagonist @entity351 (1   mg/kg intraperitoneally, 30   min before SA session). In the microdialysis studies, we observed that @entity14512 (0.1-1.0   mg/kg iv) preferentially stimulates NAc shell as compared to the NAc core. NAc shell DA increased by about 25% over basal value at the highest doses tested (0.5 and 1.0   mg/kg iv). The results obtained suggest that the eCB system, via @entity14512 , plays an important role in reward.

Endocannabinoid XXXX Self-Administration by @entity35 and Stimulation of in vivo @entity935 Transmission in the Nucleus Accumbens Shell.

@entity2366 :: ('CHEBI:41847', 'Chemical') :: ['diacylglycerol'] @entity14512 :: ('CHEBI:52392', 'Chemical') :: ['2-AG'] @entity13677 :: ('25248(Tax:10116)', 'Gene') :: ['CB1'] @entity9394 :: ('MESH:C094503', 'Chemical') :: ['2-Arachidonoylglycerol'] @entity935 :: ('MESH:D004298', 'Chemical') :: ['dopamine'] @entity9393 :: ('MESH:C078814', 'Chemical') :: ['anandamide'] @entity460 :: ('MESH:D002118', 'Chemical') :: ['calcium'] @entity35 :: ('10116', 'Species') :: ['Sprague-Dawley rats', 'Rats', 'rats'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphoinositides'] @entity351 :: ('MESH:C089032', 'Chemical') :: ['rimonabant']
@entity9394 :: (MESH:C094503,Chemical) :: ['2-Arachidonoylglycerol']
