Inhibition of glycine transporter-1 reduces cue-induced nicotine-seeking, but does not promote extinction of conditioned nicotine cue responding in the rat

• DOI: 10.1111/adb.12049
• Publication Date: 2013-03-14T21:58:36Z
• Authors: Luigi Cervo; Angelo Di Clemente; Alessandro Orrù; Federico Moro; Chiara Cassina; Emilio Merlo Pich; Mauro Corsi; Alessandro Gozzi; Angelo Bifone
• Keywords: Extinction (optical mineralogy); Self-administration

Pharmacological stimulation of N-methyl-D-aspartate receptors (NMDAr) could enhance the outcome cue-exposure therapy for smoking cessation. NMDAr can be achieved by increasing pharmacologically synaptic levels glycine, a necessary co-agonist. Here, we evaluate effects SSR504734, selective inhibitor glycine type I transporter (GlyT1) in an extinction-reinstatement procedure inducing robust and lasting nicotine-seeking behavior rats. Male Wistar rats were trained to associate discriminative stimuli (SDs) with availability nicotine (0.03 mg/kg/65 μL/2 second/infusion) or sucrose (45-mg pellet) versus non-reward two-lever operant cages. Reinforced response was followed cue signaling 20-second time-out (CSs). Once training criterion met, underwent extinction lever presses, absence reinforcers, SDs CSs. Re-exposure SD+/CS+, but not SD−/CS−, revived responding at previously reinforced lever. Acute pre-treatment SSR504734 (10 mg/kg i.p.) reduced sucrose-seeking without influencing rats' locomotor activity. Sub-chronic treatment i.p. 5 days) during daily exposure SD+/CS+ nicotine-seeking; however, this effect transient, return 72 hours. Full recovery observed after 1 month suggesting that sub-acute did engage long-term plasticity mechanisms probably involved nicotine-seeking. In conclusion, GlyT1-inhibitors might offer therapeutic opportunity acute cue-controlled nicotine-seeking, lack persistent sub-chronic associated cues suggests short-term administration GlyT1-inhibitor is sufficient promote nicotine-cue conditioned responding.