Chronic treatment with I‐dopa plus carbidopa in hemitransected rats: Preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity

Abstract

Chronic i. p. treatment with 1-dopa-carbidopa for 3 weeks in hemitransected male rats leads on one hand to tolerance to l-dopa induced turning behaviour and on the other hand to behavioural and biochemical signs of dopamine (DA) receptor supersensitivity on the intact side. Thus, the apomorphine induced ipsilateral turning behaviour is enhanced and the K_d values of the ³H-spiperone binding sites linked to DA receptors of the D₂ type on the intact, but not on the denervated side are reduced by 40%. However, the number of ³H-spiperone binding sites is reduced by 20% in striatal membranes on the intact side after this type of treatment. Therefore, chronic treatment with a catecholamine (CA) precursor leads to selective adaptive changes at intact striatal DA synapses with certain signs of the expected development of DA receptor subsensitivity, but above all with signs of paradoxical development of DA receptor supersensitivity. A hypothesis is introduced to explain these results.