Neuronal damage and changes in the expression of muscarinic acetylcholine receptor subtypes in the neonatal rat cerebral cortical upon exposure to sparteine, a quinolizidine alkaloid

Sparteine is a quinolizidine alkaloid (QA) produced by Lupine species that has generated much interest due to its anti-hypertensive, anti-pyretic, and anti-inflammatory properties. In the nervous system, sparteine has been shown to display anti-cholinergic and depressive activity, although how sparteine exerts its toxic effects in the brain remains unclear. We have addressed this issue by administering subcutaneous injections of sparteine (25 mg/kg of body weight) to rats on postnatal days 1 and 3, and then examining the expression of the muscarinic acetylcholine receptor (mAChR) subunits m1–m4 in the brains of the neonatal rats 14–60 days later. Administration of sparteine to neonatal rats caused neuronal damage in the cerebral motor cortex accompanied by transient changes in the expression of m1–m4 mAChR subunits as revealed by both RT-PCR and Western blotting. This effect could be prevented by pre-treatment with atropine (10 mg/kg) 1 h prior to the injection of sparteine, suggesting that the cytotoxic activity of sparteine is mediated through mAChRs.