title: Partial lesion of dopamine neurons of rat substantia nigra impairs conditioned place aversion but spares conditioned place preference.
abstract: Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3μg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200μg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning. Control experiments demonstrated that these lesions did not impair motor performance and did not alter the hedonic value of the sucrose and quinine. The number of dopamine neurons in the caudal part of the SNc positively correlated with the CPP scores of the 6-OHDA rats and negatively correlated with CPA scores of the SHAM rats. In addition, the CPA scores of the 6-OHDA rats positively correlated with the tissue content of striatal dopamine. Insomuch as reward-driven learning depends on an increase in dopamine release by nigral neurons, these findings show that this mechanism is functional even in rats with a partial lesion of the SNc. On the other hand, if aversion-driven learning depends on a reduction of extracellular dopamine in the striatum, the present study suggests that this mechanism is no longer functional after the partial SNc lesion.
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil.
authors.forename: Bernardo F C
authors.initials: BF
authors.lastname: Lima
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil.
authors.forename: Daniele C
authors.initials: DC
authors.lastname: Ramos
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil.
authors.forename: Janaína K
authors.initials: JK
authors.lastname: Barbiero
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil.
authors.forename: Laura
authors.initials: L
authors.lastname: Pulido
authors.affiliation: Department of Psychology, University of Sheffield, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Redgrave
authors.affiliation: Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27599-7178, USA.
authors.forename: Donita L
authors.initials: DL
authors.lastname: Robinson
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gómez-A
authors.affiliation: Departamento de Farmacologia, Universidade Federal do Paraná, Curitiba 81.530-980, PR, Brazil. Electronic address: dacunha.claudio@gmail.com.
authors.forename: Claudio
authors.initials: C
authors.lastname: Da Cunha
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects; D059290:Dopaminergic Neurons / Q000187:drug effects; D008297:Male; D009434:Neural Pathways / Q000187:drug effects; D009474:Neurons / Q000187:drug effects; D016627:Oxidopamine / Q000494:pharmacology; D017208:Rats, Wistar; D012201:Reward; D013378:Substantia Nigra / Q000187:drug effects
chemical_list: D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
keywords: basal ganglia; dopaminergic neurons; incentive salience; mesolimbic dopamine; motivation; procedural memory