Related Experiment Videos
Circling behavior in rats with 6-hydroxydopamine or electrolytic nigral lesions,
Abstract:
Unilateral destruction of dopaminergic cell bodies in the substantia nigra zona compacta (SNC) was performed in rats using either electrocoagulation or chemical lesioning (6-hydroxydopamine, 6-OHDA). Neostriatal dopamine concentration ipsilateral to an electrolytic lesion was 34% of the contralateral side 2-3 weeks after operation; serotonin and noradrenaline brain levels were not altered. In contrast, dopamine and noradrenaline forebrain concentrations ipsilateral to a 6-OHDA lesion were 20 and 31%, respectively, of the contralateral side. After 6-OHDA, dopamine concentrations in the ipsilateral neostriatum were reduced to levels below the sensitivity of the fluorometric assay; cortical, brainstem and neostriatal serotonin levels, on the other hand, were not altered after 6-OHDA. Ipsilateral circling behavior was elicited by d-amphetamine after electrolytic and chemical lesioning. In contrast, the direction of circling produced after apomorphine differed between the two lesion models: contralateral circling behavior was exhibited by 6-OHDA-lesioned rats, whereas ipsilateral circling was produced in animals with electrolytic lesions. Contralateral circling was induced in both lesion-type models by haloperidol or pimozide. S.c. atropine administration induced ipsilateral circling in rats with 6-OHDA lesions, whereas contralateral circling was observed after arecoline. Animals with electrolytic SNC lesions turn ipsilaterally after s.c. administrations of either arecoline or atropine. The data indicate that the electrolytic and 6-OHDA circling behavior models represent two different neuropharmacological states and it is, therefore, suggested that comparisons of data obtained from models using different methods of lesioning be made with caution.
Insights
Electrolytic and 6-hydroxydopamine (6-OHDA) lesions of the substantia nigra zona compacta (SNC) create distinct neuropharmacological states in rats. Researchers caution against comparing data from these different lesion models due to differing circling behaviors.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- Unilateral dopaminergic cell body destruction in the substantia nigra zona compacta (SNC) is a common method for creating animal models of Parkinson's disease.
- Two primary methods, electrocoagulation and 6-hydroxydopamine (6-OHDA) chemical lesioning, are used to achieve this destruction.
Purpose of the Study:
- To investigate and compare the neurochemical and behavioral outcomes of electrolytic versus 6-OHDA lesions in the rat SNC.
- To determine if these two lesioning methods produce comparable or distinct neuropharmacological states.
Main Methods:
- Unilateral SNC lesions were induced in rats via electrocoagulation or 6-OHDA administration.
- Neurotransmitter concentrations (dopamine, serotonin, noradrenaline) were measured in brain regions ipsilateral and contralateral to the lesion.
- Circling behavior was assessed after administration of various dopaminergic agents (d-amphetamine, apomorphine) and anticholinergic drugs (atropine, arecoline).
Main Results:
- Electrolytic lesions significantly reduced ipsilateral neostriatal dopamine, while sparing serotonin and noradrenaline.
- 6-OHDA lesions reduced both dopamine and noradrenaline in forebrain regions, with dopamine levels falling below assay sensitivity.
- Circling behavior responses to apomorphine, arecoline, and atropine differed significantly between the two lesion types, indicating distinct neuropharmacological profiles.
Conclusions:
- Electrolytic and 6-OHDA lesioning of the SNC result in different neurochemical alterations and distinct behavioral responses to pharmacological challenges.
- These findings suggest that the two models represent different neuropharmacological states.
- Caution is advised when comparing data derived from studies employing these different lesioning methodologies.