Postsynaptic Supersensitivity after 6‐Hydroxy‐dopamine Induced Degeneration of the Nigro‐striatal Dopamine System

TLDR

Postsynaptic supersensitivity after degeneration of the nigro‑striatal DA system is probably an important reason for the effectiveness of the L‑DOPA therapy against Parkinson's disease. The study examined the effects of L‑DOPA and apomorphine on rats with unilateral nigrostriatal degeneration induced by 6‑hydroxydopamine. They induced unilateral nigrostriatal degeneration in rats via intracerebral 6‑hydroxydopamine injection and assessed the effects of L‑DOPA and apomorphine by recording rotational behavior with a rotameter. Both L‑DOPA and apomorphine induced strong rotational behavior, revealing that the denervated striatum was more sensitive to DA receptor stimulation; this supersensitivity required L‑DOPA conversion to DA, could be enhanced by ro4‑4602 inhibition, and was also induced by a single reserpine dose, peaking on day 3 and declining by day 4.

Abstract

Abstract The effect of L‐DOPA and the dopamine (DA) receptor stimulating drug apomorphine was studied in rats after unilateral degeneration of the nigrostriatal DA system by intracerebral injection of 6‐hydroxydopamine. Both apomorphine and L‐DOPA induced a strong rotational behaviour which was registered in a specially designed “rotameter”. The direction of the rotation indicated that the denervated striatum was more sensitive to DA receptor stimulating drugs than the innervated striatum. This supersensitivity probably corresponded to the decentralisation type of supersensitivity in the peripheral nervous system although it developed faster. The action of L‐DOPA was inhibited by pretreatment with the DOPA‐decarboxylase inhibitor Ro4–4602 which indicated that L‐DOPA must be converted to DA in order to stimulate the supersensitive postsynaptic cells. Pretreatment with a single dose of reserpine also induced supersentitivity to apomorphine which reached its maximum on the 3rd day and then decreased on the 4th day. Postsynaptic supersensitivity after degeneration of the nigro‐striatal DA system is probably an important reason for the effectiveness of the L‐DOPA therapy against Parkinson's disease.