Bee Venom Alleviates Motor Deficits and Modulates the Transfer of Cortical Information through the Basal Ganglia in Rat Models of Parkinson's Disease

PLoS One. 2015 Nov 16;10(11):e0142838. doi: 10.1371/journal.pone.0142838. eCollection 2015.

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.

Trial registration: ClinicalTrials.gov NCT01341431.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Basal Ganglia / drug effects
  • Basal Ganglia / physiopathology*
  • Bee Venoms / administration & dosage
  • Bee Venoms / pharmacology*
  • Bee Venoms / therapeutic use
  • Catalepsy / complications
  • Catalepsy / drug therapy
  • Catalepsy / physiopathology
  • Disease Models, Animal*
  • Dopamine Antagonists / pharmacology
  • Electric Stimulation
  • Haloperidol
  • Male
  • Motor Activity / drug effects*
  • Motor Cortex / drug effects
  • Motor Cortex / physiopathology*
  • Oxidopamine
  • Parkinson Disease / complications
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology*
  • Rats, Wistar
  • Receptors, Dopamine / metabolism
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiopathology

Substances

  • Bee Venoms
  • Dopamine Antagonists
  • Receptors, Dopamine
  • Oxidopamine
  • Haloperidol

Associated data

  • ClinicalTrials.gov/NCT01341431

Grant support

This work was supported by the Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU) and by a grant from Association France Parkinson (Grand Appel d’Offre 2011). This work has been carried out within the context of the DHUNE project thanks to the support of the A*MIDEX project (n° ANR-11-IDEX-0001-02) funded by the « Investissements d’Avenir » French Government program, managed by the French National Research Agency (ANR). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.