Subacute l-DOPA in mice: Biochemical and behavioural effects

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Abstract
Mice, pretreated orally with l-DOPA (200 mg/kg) plus benserazide (50 mg/kg) (l-DOPA-B) responded when challenged 24h later with the same drug combination, with significantly greater locomotor stimulation than animals pretreated with the vehicle. The enhanced response was not due to an intrinsic effect of benserazide. Nor was it dependent on a change in central dopamine (DA) receptor sensitivity, because the two pretreatment groups (l-DOPA-B and vehicle) did not differ in their locomotor response to a range of apomorphine doses (300–3,000 μg/kg, IP). The enhanced response was, however, due to DA receptor stimulation because it was antagonised by premedication of the mice with haloperidol or pimozide. Moreover, the enhanced response to l-DOPA-B challenge was also produced when mice were pretreated (24h earlier) with a high dose of l-DOPA alone (without benserazide) (1,200 mg/kg, orally). Animals which had been pretreated with l-DOPA-B had significantly higher brain levels of l-DOPA and DA after a subsequent challenge dose of l-DOPA-B administered 24h later. Thus the enhanced response to l-DOPA-B observed in the present experiment appears to be dependent on some mechanism which produces higher concentrations of l-DOPA (and consequently DA) in the brain.