Relationship between L-DOPA-induced reduction in motor and exploratory activity and degree of DAT binding in the rat

Abstract

Purpose: The present study assessed the influence of L-DOPA administration on neostriatal dopamine (DA) transporter (DAT) binding in relation to motor and exploratory behaviors in the rat.Methods: Rats received injections of 5 mg/kg L-DOPA, 10 mg/kg L-DOPA or vehicle. Motor and exploratory behaviors were assessed for 30 min in an open field prior to administration of [123I]FP-CIT. Dopamine transporter binding was measured with small animal single-photon emission computed tomography (SPECT) 2 h after radioligand administration for 60 min.Results: Both L-DOPA doses significantly reduced DAT binding and led to significantly less head-shoulder motility and more sitting relative to vehicle. Moreover, 10 mg/kg L-DOPA induced less distance traveled and ambulation than 5 mg/kg L-DOPA. Analysis of time-behavior (t-b) curves showed that L-DOPA-treated animals relative to vehicle exhibited (1) a faster rate of increase in duration of sitting; (2) a slower rate of increase in duration of head-shoulder motility; and (3) a slower rate of decrease in frequency of head-shoulder motility.Conclusions: The reductions of striatal DAT binding after L-DOPA challenges reflected elevated concentrations of synaptic DA. L-DOPA-treated animals showed less head-shoulder motility and more sitting than vehicle-treated animals, indicating an association between less behavioral activity and increased availability of striatal DA. The faster increase of sitting duration to a higher final level and the slower increase of head-shoulder motility to a lower final level relative to controls may be interpreted in terms on behavioral habituation to a novel environment.

Nitrosative and cognitive effects of chronic l-DOPA administration in rats with intra-nigral 6-OHDA lesion

“…Some reports have shown that L-DOPA administration in adult rats induces hypoactivity (McDevitt and Setler, 1981;Grigoriadis et al, 1996;Nikolaus et al, 2014). These studies show that this behavior depends on reductions in the striatal DAT binding which suggest elevated concentrations of synaptic DA (Nikolaus et al, 2014) that may activate the dopaminergic presynaptic D2 receptors.…”

“…Some reports have shown that L-DOPA administration in adult rats induces hypoactivity (McDevitt and Setler, 1981;Grigoriadis et al, 1996;Nikolaus et al, 2014). These studies show that this behavior depends on reductions in the striatal DAT binding which suggest elevated concentrations of synaptic DA (Nikolaus et al, 2014) that may activate the dopaminergic presynaptic D2 receptors. These receptors modulate spontaneous activity by modulating DA release into basal ganglia, (Grigoriadis et al, 1996), since activation of the D2 receptor inhibits the release of DA and decreases motor activity (Gessa et al, 1985).…”

DAT versus D2 receptor binding in the rat striatum: l‐DOPA‐induced motor activity is better predicted by reuptake than release of dopamine

“…DAT and D 2 R imaging studies were performed as previously described (Nikolaus et al, 2014a, 2016b). Thirty min postchallenge and immmiately following the behavioral trials, animals received i.p.…”

“…Neostriatal DAT binding is influenced by treatment with compounds that increase synaptic DA levels in healthy animals as well as in animal models of PD with subtotal DAergic depletion (for reviews see Winogrodzka et al, ; Nikolaus et al, ). We have recently demonstrated that challenge with 5 and 10 mg/kg l ‐DOPA significantly reduced both neostriatal DAT‐ and D 2 R‐binding in healthy rats relative to baseline and vehicle by 20–30% (Nikolaus et al, 2014a, 2016b).…”

“…We have assessed neostriatal DAT and D 2 R binding in rats in conjunction with motor and exploratory behaviors after 5 and 10 mg/kg l ‐DOPA or vehicle (Nikolaus et al, 2014a, 2016b). Interestingly, individual behavioral parameters correlated significantly with D 2 R binding after both l ‐DOPA doses but not after vehicle, whereas significant correlations were found between motor/exploratory behaviors and DAT binding after vehicle and 5 mg/kg, but not after 10 mg/kg l ‐DOPA.…”