title: SLV330, a cannabinoid CB(1) receptor antagonist, attenuates ethanol and nicotine seeking and improves inhibitory response control in rats.
abstract: Cannabinoid CB(1) receptor (CB(1)R) signaling has been shown to play a role in the regulation of addictive behavior. In the present study, our aim was to investigate whether the CB(1)R antagonist SLV330 could reduce ethanol and nicotine self-administration and cue-induced reinstatement of ethanol and nicotine seeking behavior in Wistar rats. In operant chambers, rats were learned to emit a specific response (nose poke) in order to receive an ethanol solution or intravenous injections of nicotine. Discrete light and tone cues were presented during ethanol and nicotine delivery. These cues are particularly important for drug self-administration behavior and, through Pavlovian conditioning, acquire conditioned reinforcing and motivational properties and are therefore able to generate and maintain drug-seeking behavior. Subsequently, the CB(1)R antagonist SLV330 (doses ranging from 1 to 10mg/kg, given orally, p.o.) was administered to investigate the effects on drug self-administration. In addition, responding for ethanol and nicotine was extinguished. Then, the animals were tested for cue-induced reinstatement of ethanol and nicotine seeking and treated with vehicle or SLV330. Finally, the effects of SLV330 were studied on the number of anticipatory responses in the 5-choice serial reaction time task (5-CSRTT) in order to determine whether this compound could also increase impulse control in Wistar rats. The CB(1) antagonist SLV330 was effective in reducing ethanol self-administration at a lowest effective dose (LED) of 10mg/kg (p.o.) and reinstatement of ethanol seeking at a LED of 3mg/kg (p.o.). SLV330 was also effective in reducing nicotine self-administration and reinstatement of nicotine seeking, although at a LED of 10mg/kg (p.o.). Finally, SLV330 decreased time delay-dependent anticipatory responding (LED of 3.0mg/kg, p.o.), indicating an increased inhibitory control. These findings are in agreement with results reported with other CB(1) antagonists. The combined action of reducing the reinforcing and motivational properties of nicotine and alcohol and the improvement of impulse control supports the idea that the cannabinoid system is a promising target for anti-relapse medication.
authors.affiliation: Abbott Healthcare Products BV, C.J. van Houtenlaan 36, 1381 CP Weesp, The Netherlands. natasja.debruin@gmail.com
authors.forename: N M W J
authors.initials: NM
authors.lastname: de Bruin
authors.forename: J H M
authors.initials: JH
authors.lastname: Lange
authors.forename: C G
authors.initials: CG
authors.lastname: Kruse
authors.forename: A H
authors.initials: AH
authors.lastname: Herremans
authors.forename: A N M
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: M
authors.initials: M
authors.lastname: van Drimmelen
authors.forename: T J
authors.initials: TJ
authors.lastname: De Vries
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects*; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012054:Reinforcement, Psychology; D012646:Self Administration; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C551035:SLV 330; D013449:Sulfonamides; D000431:Ethanol; D009538:Nicotine