The effect of a subchronic post-lesion treatment with (-)-deprenyl on the sensitivity of 6-OHDA-lesioned rats to apomorphine and d-amphetamine.
The effects of a subchronic post-lesion treatment of 14 days with (-)-deprenyl or its solvent on the rotational response to apomorphine (0.1 mg/kg) and d-amphetamine (2.5 mg/kg) in 6-OHDA- and SHAM-lesioned rats were investigated. Rats received a local injection of 6-OHDA (9 microg/0.7 microl) or its solvent into the medial forebrain bundle. Following the (SHAM or 6-OHDA) lesion the animals were randomly assigned to one of the two post-lesion treatment groups, viz. vehicle or (-)-deprenyl (0.1 mg/kg, 2 x day, i.p.) and treated for 14 days. After a wash out period of 6 weeks the number of rotations in response to apomorphine (0.1 mg/kg) and d-amphetamine (2.5 mg/kg) were compared. Seven days following the final behavioural experiments the animals were sacrificed and the striatal dopamine, DOPAC and HVA levels were determined. The (-)-deprenyl-treated 6-OHDA-lesioned rats responded with a reduced number of rotations in response to apomorphine but not to d-amphetamine as compared to vehicle-treated 6-OHDA-lesioned rats. However the two lesion groups did not differ in striatal dopamine, DOPAC and HVA concentrations; the levels were below or close to the detection limit ipsilateral to the 6-OHDA injections. Thus a post-lesion treatment with (-)-deprenyl reduced the dopaminergic supersensitivity without a concomitant increase in striatal dopamine content. The data are discussed in the light of the previously described neurorescue properties of (-)-deprenyl.
Spooren
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WP
Novartis Pharma Inc., Nervous System, Basel, Switzerland.
Waldmeier
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P
Gentsch
C
C
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D018663:Adrenergic Agents; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000494:pharmacology*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000008:administration & dosage*
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D015259:Dopamine Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D016627:Oxidopamine; D000661:Amphetamine; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid