title: Anterior ventral tegmental area dopaminergic neurons are not involved in the motivational effects of bromocriptine, pramipexole and cocaine in drug-free rats.
abstract: Dopamine dysregulation syndrome in Parkinson's disease has been attributed to dopamine replacement therapies and/or a lesion of the dopaminergic system. Dopaminergic neuronal loss targets the substantia nigra and the ventral tegmental area (VTA). We hypothesize that dopamine replacement therapy is responsible for the potential reinforcement effect in Parkinson's disease, by acting on the neuronal reward circuitry. We previously demonstrated that the posterior (p) VTA, which projects to the nucleus accumbens (NAc), is implicated in the motivational effect of dopamine receptor agonists in 6-OHDA bilateral pVTA-lesioned drug-free animals. In the present study we investigated the implication of the anterior (a) VTA in the potential reinforcement effect of dopamine receptor agonists. Using the conditioned place preference (CPP) behavioral paradigm, we investigated the motivational effects of dopamine receptor agonists (bromocriptine and pramipexole), and cocaine in rats with a 6-OHDA bilateral lesion of the aVTA. Bromocriptine and pramipexole did not induce a significant CPP at 1mg/kg in both sham and bilateral 6-OHDA-lesioned rats. However bromocriptine induced CPP only at a dose of 3mg/kg in both animal groups. Moreover cocaine, which is known to increase dopamine release, induced reinforcing effects in both 6-OHDA-lesioned and sham rats. Our data show a lack of involvement of aVTA dopamine neurons in the motivational effects of bromocriptine, pramipexole and cocaine.
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France.
authors.forename: Omar
authors.initials: O
authors.lastname: Ouachikh
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France.
authors.forename: Wisam
authors.initials: W
authors.lastname: Dieb
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France; CHU Clermont-Ferrand, Service de Neurologie, 63000 Clermont-Ferrand, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Durif
authors.affiliation: Clermont Université, Université d'Auvergne, EA7280, Laboratoire de Neuropsychopharmacologie des systèmes dopaminergiques sous corticaux, Clermont-Ferrand, France. Electronic address: azhafidi@univ-bpclermont.fr.
authors.forename: Aziz
authors.initials: A
authors.lastname: Hafidi
mesh_terms: D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology*; D001971:Bromocriptine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology*; D059290:Dopaminergic Neurons / Q000187:drug effects*; D008297:Male; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009043:Motor Activity / Q000187:drug effects; D000077487:Pramipexole; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
chemical_list: D052160:Benzothiazoles; D018491:Dopamine Agonists; D001971:Bromocriptine; D000077487:Pramipexole; D003042:Cocaine
keywords: 6-OHDA; Conditioned place preference; Parkinson; Reward