Metabotropic glutamate receptor (mGluR5) antagonist MPEP attenuated cue- and schedule-induced reinstatement of nicotine self-administration behavior in rats.
Previous studies suggested that metabotropic glutamate 5 (mGlu5) receptors play an important role in the reinforcing effects of abused drugs. The present experiments evaluated the effects of the mGlu5 receptor antagonist, MPEP (2-methyl-6-(phenylethynyl)-pyridine hydrochloride; 1-10 mg/kg, salt, i.p.), in rat models of nicotine-seeking behavior that may have relevance to relapse to drug-taking. Male Wistar rats (with restricted access to food) were trained to nose-poke to receive intravenous infusions of nicotine (0.03 mg/kg per infusion, base) under a fixed ratio 5 time out 60 s schedule of reinforcement. After stable nicotine self-administration was acquired, nose-poking behavior was extinguished in the absence of nicotine-associated cues. During the reinstatement test phase, independent groups of animals were exposed to: (a) response-contingent nicotine-associated cues (cue-induced reinstatement); or (b) response-noncontingent presentations of 45-mg food pellets under fixed time 2 min schedule (schedule-induced reinstatement). Additional control experiments were conducted to demonstrate that in nicotine-naïve animals MPEP does not affect cue-induced reinstatement of food-seeking behavior and has no effects on operant behavior maintained by a simple fixed interval 2 min schedule of food reinforcement. Pretreatment with MPEP (10 mg/kg) significantly attenuated the reinstatement of nicotine-seeking in both experiments. Further, MPEP (10 mg/kg) significantly attenuated polydipsia induced by a fixed time 2 min food schedule. In conclusion, the present findings indicate that the blockade of mGlu5 receptors attenuates cue-induced reinstatement of nicotine self-administration behavior (but not food-seeking) and may produce a general inhibition of schedule-induced behaviors, including schedule-induced nicotine-seeking.
Bespalov
Anton Y
AY
Institute of Pharmacology, Pavlov Medical University, St. Petersburg, Russia. anton.bespalov@abbott.com
Dravolina
Olga A
OA
Sukhanov
Ilya
I
Zakharova
Elena
E
Blokhina
Elena
E
Zvartau
Edwin
E
Danysz
Wojciech
W
van Heeke
Gino
G
Markou
Athina
A
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D005502:Food; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000037:antagonists & inhibitors*; D012055:Reinforcement Schedule; D012646:Self Administration
C578937:Grm5 protein, rat; D018722:Nicotinic Agonists; D011725:Pyridines; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D009538:Nicotine; C121465:6-methyl-2-(phenylethynyl)pyridine