Cholinergic transmission may play an important role in the mediation of drug addiction. Acethylcholine esterase (AChE) inhibitors (AChE-I) by increasing acethylcholine brain concentrations may offers a feasible tool to better understand the role of ACh in drug addiction behaviours. The aim of the series of experiments here described is to study the effect of AChE-I tacrine on three protocols of nicotine or d-amphetamine addictive behaviour in Sprague Dawley rats: drug discrimination, drug self administration and extinction responding. When different groups of rats met the criteria for d-amphetamine (0.6 mg/Kg IP) or nicotine (0.2 mg/Kg SC) discrimination from vehicle in a two-lever drug discrimination task, tacrine (1.25 mg/Kg, IP) was tested for generalization. The effect of tacrine pre-treatment (0.32 mg/Kg IV) on nicotine or amphetamine reinforcing properties was studied in two groups of rats trained to a schedule of FR2:d-amphetamine (0.1 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) IV self administration (1-h session). Finally, tacrine (0.32 mg/Kg IV) effect on responding on first extinction session was tested when amphetamine or nicotine IV infusions were omitted. Nicotine or amphetamine discriminative stimulus did not generalize with tacrine. Tacrine pre-treatment did not induce any change on nicotine or amphetamine self-administration. However, when given on the first day of extinction, tacrine induced a significant decrease of nicotine-paired (-63%, P<0.05) and a trend to decrease of amphetamine-paired (-50%, P=0.06 ) -lever responding vs. corresponding baseline. These findings showed that inhibition of AChE with tacrine did not change interoceptive and reinforcing stimuli properties of nicotine or amphetamine, but suggest a potential inhibitory effect on learning of the extinction responding. Further studies are needed to test tacrine on reinstatement to amphetamine or nicotine-seeking behaviour.

Acethylcholine esterase inhibitor tacrine reduced extinction responding, but not self-administration and drug discrimination, of nicotine or amphetamine in rats

AUBER, Alessia;TEDESCO, Vincenzo;FUMAGALLI, Guido Francesco;CHIAMULERA, Cristiano
2009-01-01

Abstract

Cholinergic transmission may play an important role in the mediation of drug addiction. Acethylcholine esterase (AChE) inhibitors (AChE-I) by increasing acethylcholine brain concentrations may offers a feasible tool to better understand the role of ACh in drug addiction behaviours. The aim of the series of experiments here described is to study the effect of AChE-I tacrine on three protocols of nicotine or d-amphetamine addictive behaviour in Sprague Dawley rats: drug discrimination, drug self administration and extinction responding. When different groups of rats met the criteria for d-amphetamine (0.6 mg/Kg IP) or nicotine (0.2 mg/Kg SC) discrimination from vehicle in a two-lever drug discrimination task, tacrine (1.25 mg/Kg, IP) was tested for generalization. The effect of tacrine pre-treatment (0.32 mg/Kg IV) on nicotine or amphetamine reinforcing properties was studied in two groups of rats trained to a schedule of FR2:d-amphetamine (0.1 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) IV self administration (1-h session). Finally, tacrine (0.32 mg/Kg IV) effect on responding on first extinction session was tested when amphetamine or nicotine IV infusions were omitted. Nicotine or amphetamine discriminative stimulus did not generalize with tacrine. Tacrine pre-treatment did not induce any change on nicotine or amphetamine self-administration. However, when given on the first day of extinction, tacrine induced a significant decrease of nicotine-paired (-63%, P<0.05) and a trend to decrease of amphetamine-paired (-50%, P=0.06 ) -lever responding vs. corresponding baseline. These findings showed that inhibition of AChE with tacrine did not change interoceptive and reinforcing stimuli properties of nicotine or amphetamine, but suggest a potential inhibitory effect on learning of the extinction responding. Further studies are needed to test tacrine on reinstatement to amphetamine or nicotine-seeking behaviour.
tacrine; extinction; self-administration
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11562/335354
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