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Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues

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Abstract

Rationale

We recently demonstrated that blocking specific nicotinic acetylcholine receptors (nAChRs) abolishes the conditioned reinforcing properties of ethanol-associated cues in rat, suggesting nAChRs as promising pharmacological targets for prevention of cue-induced relapse.

Objectives

The present study investigated the involvement of nAChR subtypes in the conditioned reinforcing properties of stimuli associated with a natural reward (sucrose).

Methods

Water-deprived rats were trained to associate a tone + light stimulus (CS) with the presentation of a 0.1 M sucrose solution for 10 consecutive days. On the subsequent day, the animals were tested on the stringent acquisition of a new instrumental response with conditioned reinforcement, following a systemic injection of the nonselective nAChR antagonist mecamylamine (MEC) or the selective α7 and α6/α3β2β3* nAChR antagonist methyllycaconitine (MLA). At testing, the rats were presented with two novel levers. Responding on the lever assigned as active (CR lever) resulted in a presentation of the CS alone, while pressing the inactive lever (NCR lever) had no programmed consequences.

Results

Control animals pressed the CR lever significantly more than the NCR lever, demonstrating that the CR had acquired conditioned reinforcing properties. Systemic MEC as well as MLA reduced the CR lever responses to the same level as for the NCR lever.

Conclusions

These results demonstrate a role for the α7 and/or α6/α3β2β3* nAChRs in conditioned reinforcement to a natural reward and suggest neuronal nAChRs as common mediators of the impact of cues on incentive processes.

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Abbreviations

nAChR:

Nicotinic acetylcholine receptor

CS:

Conditioned stimulus

US:

Unconditioned stimulus

MEC:

Mecamylamine

MLA:

Methyllycaconitine citrate

CR:

Conditioned reinforcement

VTA:

Ventral tegmental area

PBS:

Phosphate-buffered saline

VR:

Variable ratio

ANOVA:

Analysis of variance

PLSD:

Protected least-significant difference

α-CtxMII:

α-Conotoxin MII

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Acknowledgements

Financial support for this work was obtained from the Swedish Medical Research Council no. 11583, the Swedish Labor Market Insurance (AFA) support for biomedical alcohol research, the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, NIDA 2 R01 10765-04A1, PHS NIH (DA15222, DA11717, and AA15632 to JRT), Gunnar och Märtha Bergendahls Stiftelse, the Council for Medical Tobacco Research - Swedish Match, Wilhelm och Martina Lundgrens vetenskapsfond, Kungliga Vetenskaps -och Vitterhets-Samhället i Göteborg, Helge Ax:son Johnsons Stiftelse, Längmanska kulturfonden, Jubileumsfonden, Iris Jonzén-Sandbloms och Greta Jonzéns Stiftelse and Stiftelsen KvinnorKan, Axel Linders stiftelse, and Apotekarsocieteten. We are grateful for the generous gift of mecamylamine and MLA from the NIDA drug supply program, Bethesda, MD, USA.

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Authors and Affiliations

  1. Addiction Biology Unit (ABU), Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden

    Elin Löf, Rosita Stomberg & Bo Söderpalm

  2. Department of Psychiatry, Division of Molecular Psychiatry, Yale University School of Medicine, New Haven, CT, USA

    Peter Olausson & Jane R. Taylor

  3. Psychiatry/SU/Sahlgrenska, Blå Stråket 15, SE-413 45, Gothenburg, Sweden

    Elin Löf

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  1. Elin Löf
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Correspondence to Elin Löf.

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Löf, E., Olausson, P., Stomberg, R. et al. Nicotinic acetylcholine receptors are required for the conditioned reinforcing properties of sucrose-associated cues. Psychopharmacology 212, 321–328 (2010). https://doi.org/10.1007/s00213-010-1957-x

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