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The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor.
Psychopharmacology (Berl). 2003 Mar; 166(3):306-13.P

Abstract

RATIONALE

Within the mammalian ventral tegmental area (VTA), nicotine produces both aversive and rewarding motivational effects. However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood.

OBJECTIVES

In the present study, we challenged the motivational effects of nicotine directly in the VTA with nAChR subunit specific antagonists.

METHODS

Using an unbiased place-conditioning procedure as a behavioural assay, we performed bilateral microinfusions of nicotine over a wide range of concentrations (0.008, 8, 24 and 48 nmol/0.5 microl) and challenged the aversive and reinforcing behavioural effects of these nicotine doses with co-administration of di-hydro-beta-erythroidine (DHbetaE) (5 or 50 nmol/0.5 microl), a nAChR antagonist with higher relative affinity for the alpha4beta2 nAChR subunit, methyllycaconitine citrate (MLA) (0.4 or 4 nmol/0.5 microl), a nAChR antagonist that displays greater relative affinity for the alpha7 nAChR, and the NMDA receptor antagonist, d-2-amino-7-phosphoheptanoic acid (AP-7; 18 nmol/0.5 microl).

RESULTS

The alpha4beta2 antagonist DHbetaE blocked both the rewarding and aversive properties of intra-VTA nicotine. However, the alpha7 antagonist MLA blocked nicotine reward and switched the motivational valence of higher doses of nicotine (8-48 nmol/0.5 microl) from rewarding to aversive. The NMDA antagonist AP-7 blocked both the aversive and rewarding effects of intra-VTA nicotine.

CONCLUSIONS

These results suggest a functional dissociation between nAChR neural substrates within the VTA that mediate the bivalent motivational properties of nicotine and further suggest that nicotine may produce its motivational effects through a glutamatergic mechanism.

Authors+Show Affiliations

Department of Anatomy and Cell Biology, Neurobiology Research Group, University of Toronto, 1 King's College Circle, M5S 1A8, Toronto, Ontario, Canada.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12569428

Citation

Laviolette, Steven R., and Derek van der Kooy. "The Motivational Valence of Nicotine in the Rat Ventral Tegmental Area Is Switched From Rewarding to Aversive Following Blockade of the Alpha7-subunit-containing Nicotinic Acetylcholine Receptor." Psychopharmacology, vol. 166, no. 3, 2003, pp. 306-13.
Laviolette SR, van der Kooy D. The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor. Psychopharmacology (Berl). 2003;166(3):306-13.
Laviolette, S. R., & van der Kooy, D. (2003). The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor. Psychopharmacology, 166(3), 306-13.
Laviolette SR, van der Kooy D. The Motivational Valence of Nicotine in the Rat Ventral Tegmental Area Is Switched From Rewarding to Aversive Following Blockade of the Alpha7-subunit-containing Nicotinic Acetylcholine Receptor. Psychopharmacology (Berl). 2003;166(3):306-13. PubMed PMID: 12569428.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The motivational valence of nicotine in the rat ventral tegmental area is switched from rewarding to aversive following blockade of the alpha7-subunit-containing nicotinic acetylcholine receptor. AU - Laviolette,Steven R, AU - van der Kooy,Derek, Y1 - 2003/02/05/ PY - 2002/08/09/received PY - 2002/10/19/accepted PY - 2003/2/6/pubmed PY - 2003/5/8/medline PY - 2003/2/6/entrez SP - 306 EP - 13 JF - Psychopharmacology JO - Psychopharmacology (Berl.) VL - 166 IS - 3 N2 - RATIONALE: Within the mammalian ventral tegmental area (VTA), nicotine produces both aversive and rewarding motivational effects. However, the specific neuronal nicotinic acetylcholine receptor (nAChR) subtypes responsible for these effects are not clearly understood. OBJECTIVES: In the present study, we challenged the motivational effects of nicotine directly in the VTA with nAChR subunit specific antagonists. METHODS: Using an unbiased place-conditioning procedure as a behavioural assay, we performed bilateral microinfusions of nicotine over a wide range of concentrations (0.008, 8, 24 and 48 nmol/0.5 microl) and challenged the aversive and reinforcing behavioural effects of these nicotine doses with co-administration of di-hydro-beta-erythroidine (DHbetaE) (5 or 50 nmol/0.5 microl), a nAChR antagonist with higher relative affinity for the alpha4beta2 nAChR subunit, methyllycaconitine citrate (MLA) (0.4 or 4 nmol/0.5 microl), a nAChR antagonist that displays greater relative affinity for the alpha7 nAChR, and the NMDA receptor antagonist, d-2-amino-7-phosphoheptanoic acid (AP-7; 18 nmol/0.5 microl). RESULTS: The alpha4beta2 antagonist DHbetaE blocked both the rewarding and aversive properties of intra-VTA nicotine. However, the alpha7 antagonist MLA blocked nicotine reward and switched the motivational valence of higher doses of nicotine (8-48 nmol/0.5 microl) from rewarding to aversive. The NMDA antagonist AP-7 blocked both the aversive and rewarding effects of intra-VTA nicotine. CONCLUSIONS: These results suggest a functional dissociation between nAChR neural substrates within the VTA that mediate the bivalent motivational properties of nicotine and further suggest that nicotine may produce its motivational effects through a glutamatergic mechanism. SN - 0033-3158 UR - https://www.unboundmedicine.com/medline/citation/12569428/The_motivational_valence_of_nicotine_in_the_rat_ventral_tegmental_area_is_switched_from_rewarding_to_aversive_following_blockade_of_the_alpha7_subunit_containing_nicotinic_acetylcholine_receptor_ L2 - https://dx.doi.org/10.1007/s00213-002-1317-6 DB - PRIME DP - Unbound Medicine ER -