β2-Subunit-containing nicotinic acetylcholine receptors are involved in nicotine-induced increases in conditioned reinforcement but not progressive ratio responding for food in C57BL/6 mice
- 371 Downloads
Nicotine administration potentiates conditioned reinforcement in rats, an effect that persists for weeks after chronic exposure. Little is known regarding the nicotinic receptor subtypes that may mediate this effect.
The purpose of this study was to determine whether β2-subunit-containing nicotinic acetylcholine receptors (β2*nAChRs) are necessary for lasting effects of nicotine on conditioned and primary reinforcement in mice.
β2 knockout (β2KO) and wild-type (WT) mice received 14 days of nicotine exposure (NIC, 200 μg/ml in 2% saccharin) or saccharin alone (SAC) in their drinking water. Five days later, mice received paired presentations of a conditioned stimulus (CS) with water unconditioned stimulus (US) or explicitly unpaired presentations of the CS and US during Pavlovian discriminative approach training. Training was followed by two conditioned reinforcement tests. Mice were subsequently tested for food-reinforced responding in the absence of explicit cues followed by a progressive ratio test.
During conditioned reinforcement testing, only mice in the paired condition showed increased responding in the CS-reinforced aperture over inactive apertures. WT-NIC mice showed enhanced conditioned reinforcement compared to WT-SAC animals. β2KO-SAC mice showed elevated conditioned reinforcement compared to WT-SAC subjects, but β2KO-NIC and β2KO-SAC mice did not differ in responding with conditioned reinforcement. Prior nicotine exposure did not alter food-reinforced responding but resulted in elevated break points for food in both genotypes.
These data show that nicotine exposure enhances conditioned reinforcement in mice and indicate that β2*nAChRs are necessary for nicotine-dependent enhancement of incentive aspects of motivation but not motivation for primary reinforcement measured by progressive ratio responding.
KeywordsLearning Reward Motivation Mouse Associative learning Pavlovian Drug
This work was supported by grants DA00436, DA14241, and AA15632 from the National Institutes of Health. We wish to thank Chris Kochevar and Elin Lof for experimental assistance and Natalie Tronson for help in modifying the behavioral software.
- Burns LH, Robbins TW, Everitt BJ (1993) Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of d-amphetamine. Behav Brain Res 55:167–183CrossRefPubMedGoogle Scholar
- Donny EC, Chaudhri N, Caggiula AR, Evans-Martin FF, Booth S, Gharib MA, Clements LA, Sved AF (2003) Operant responding for a visual reinforcer in rats is enhanced by noncontingent nicotine: implications for nicotine self-administration and reinforcement. Psychopharmacology (Berl) 169:68–76CrossRefGoogle Scholar
- Grady SR, Meinerz NM, Cao J, Reynolds AM, Picciotto MR, Changeux JP, McIntosh JM, Marks MJ, Collins AC (2001) Nicotinic agonists stimulate acetylcholine release from mouse interpeduncular nucleus: a function mediated by a different nAChR than dopamine release from striatum. J Neurochem 76:258–268CrossRefPubMedGoogle Scholar
- King SL, Marks MJ, Grady SR, Caldarone BJ, Koren AO, Mukhin AG, Collins AC, Picciotto MR (2003) Conditional expression in corticothalamic efferents reveals a developmental role for nicotinic acetylcholine receptors in modulation of passive avoidance behavior. J Neurosci 23:3837–3843PubMedGoogle Scholar
- Mackintosh N (1974) The psychology of animal learning. Academic, New YorkGoogle Scholar
- Marubio LM, Gardier AM, Durier S, David D, Klink R, Arroyo-Jimenez MM, McIntosh JM, Rossi F, Champtiaux N, Zoli M, Changeux JP (2003) Effects of nicotine in the dopaminergic system of mice lacking the alpha4 subunit of neuronal nicotinic acetylcholine receptors. Eur J Neurosci 17:1329–1337CrossRefPubMedGoogle Scholar
- Parkinson JA, Olmstead MC, Burns LH, Robbins TW, Everitt BJ (1999) Dissociation in effects of lesions of the nucleus accumbens core and shell on appetitive pavlovian approach behavior and the potentiation of conditioned reinforcement and locomotor activity by d-amphetamine. J Neurosci 19:2401–2411PubMedGoogle Scholar
- Taylor JR, Jentsch JD (2001) Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4-methylenedioxymethamphetamine (“Ecstasy”). Biol Psychiatry 50:137–143CrossRefPubMedGoogle Scholar
- Yin X, Cui W, Hu G, Wang H (2004) Desensitization of alpha7 nicotinic receptors potentiated the inhibitory effect on M-current induced by stimulation of muscarinic receptors in rat superior cervical ganglion neurons. J Neural Transm (in press). DOI 10.1007/s0070200402606Google Scholar