title: Long-term restorative effects of bromocriptine on operant responding in the 6-hydroxydopamine-lesioned rat.
abstract: Despite recent recognition of the complexity of the motor and nonmotor dysfunctions that manifest in Parkinson's disease, the propensity of drugs to alleviate the dopamine-dependent symptoms in the 6-hydroxydopamine rat model is still typically being assessed using relatively simple measures of motor function. We investigated the ability of the D2 agonist, bromocriptine, to ameliorate impairments in a more complex operant task, which simultaneously assessed both motor and nonmotor deficits. Rats were trained on a lateralized choice reaction time task that has previously been found to be sensitive to dopamine depletion. One subgroup of rats was then given unilateral 6-hydroxydopamine lesions of the medial forebrain bundle. Once they exhibited stable postlesion deficits, the rats in the lesion group were administered bromocriptine (1.25 mg/kg) 120 min before testing. Bromocriptine induced a transient improvement in motor function but most notably produced a persistent improvement in the accuracy of performance in the task. The improvement in response initiation and selection persisted on testing in the absence of bromocriptine and was not reversed by the D2 antagonist, raclopride (0.2 mg/kg). These results may reflect a conditioning effect of bromocriptine on operant behaviour.
authors.affiliation: aBrain Repair Group, School of Biosciences bSchool of Pharmacy and Pharmaceutical Sciences, Cardiff University, Cardiff cEli Lilly and Co. Ltd, Surrey, UK.
authors.forename: Ellen M
authors.initials: EM
authors.lastname: Murphy
authors.forename: Mariah J
authors.initials: MJ
authors.lastname: Lelos
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Neill
authors.forename: Emma L
authors.initials: EL
authors.lastname: Lane
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Dunnett
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001971:Bromocriptine / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects*; D018491:Dopamine Agonists / Q000627:therapeutic use*; D008297:Male; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011930:Reaction Time
chemical_list: D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D001971:Bromocriptine; D016627:Oxidopamine