title: Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease.
abstract: Recent evidence points to a neuroprotective action of bee venom on nigral dopamine neurons in animal models of Parkinson's disease (PD). Here we examined whether bee venom also displays a symptomatic action by acting on the pathological functioning of the basal ganglia in rat PD models. Bee venom effects were assessed by combining motor behavior analyses and in vivo electrophysiological recordings in the substantia nigra pars reticulata (SNr, basal ganglia output structure) in pharmacological (neuroleptic treatment) and lesional (unilateral intranigral 6-hydroxydopamine injection) PD models. In the hemi-parkinsonian 6-hydroxydopamine lesion model, subchronic bee venom treatment significantly alleviates contralateral forelimb akinesia and apomorphine-induced rotations. Moreover, a single injection of bee venom reverses haloperidol-induced catalepsy, a pharmacological model reminiscent of parkinsonian akinetic deficit. This effect is mimicked by apamin, a blocker of small conductance Ca2+-activated K+ (SK) channels, and blocked by CyPPA, a positive modulator of these channels, suggesting the involvement of SK channels in the bee venom antiparkinsonian action. In vivo electrophysiological recordings in the substantia nigra pars reticulata (basal ganglia output structure) showed no significant effect of BV on the mean neuronal discharge frequency or pathological bursting activity. In contrast, analyses of the neuronal responses evoked by motor cortex stimulation show that bee venom reverses the 6-OHDA- and neuroleptic-induced biases in the influence exerted by the direct inhibitory and indirect excitatory striatonigral circuits. These data provide the first evidence for a beneficial action of bee venom on the pathological functioning of the cortico-basal ganglia circuits underlying motor PD symptoms with potential relevance to the symptomatic treatment of this disease.
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Maurice
authors.affiliation: Aix Marseille Université, CNRS, LNC UMR 7291, Marseille, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Deltheil
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Melon
authors.affiliation: INSERM, CNRS, Collège de France, CIRB UMR 7241 U-1050, Paris, France.|APHP, Département des Maladies du Système Nerveux, Centre Expert Inter-Régional Ile de France de la Maladie de Parkinson, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Bertrand
authors.initials: B
authors.lastname: Degos
authors.affiliation: Aix Marseille Université, CNRS, LNC UMR 7291, Marseille, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Mourre
authors.affiliation: Aix Marseille Université, CNRS, LNC UMR 7291, Marseille, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Amalric
authors.affiliation: Aix Marseille Université, CNRS, IBDM UMR 7288, Marseille, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Kerkerian-Le Goff
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology*; D001514:Bee Venoms / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D002375:Catalepsy / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004558:Electric Stimulation; D006220:Haloperidol; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009044:Motor Cortex / Q000187:drug effects / Q000503:physiopathology*; D016627:Oxidopamine; D010300:Parkinson Disease / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology*; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000503:physiopathology
chemical_list: D001514:Bee Venoms; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D016627:Oxidopamine; D006220:Haloperidol