Invariance of the density of dopamine uptake sites and dopamine metabolism in the rat brain after a chronic treatment with the dopamine uptake inhibitor GBR 12783

Abstract

Summary.A chronic treatment (10 mg/kg, twice daily during 9 days) with the dopamine uptake inhibitor GBR 12783 was performed in rats at a dose increasing their locomotor activity.Forty-eight hours after the last administration, animals were sacrificed and 3H mazindol binding was performed on brain slices. Autoradiographic analysis revealed no change in this binding relatively to control animals in regions with high dopamine contents: striatum, nucleus accumbens, olfactory tubercle, substantia nigra and ventral tegmentum area. The treatment did not either modify the levels of dopamine (DA) and metabolites (HVA, DOPAC) both in the striatum and the nucleus accumbens. Thus, early after the end of the treatment, the chronic blockade of the dopamine uptake complex regulates neither the dopamine uptake complex nor the dopamine metabolism.

Preferential Vulnerability of Nucleus Accumbens Dopamine Binding Sites to Low‐Level Lead Exposure: Time Course of Effects and Interactions with Chronic Dopamine Agonist Treatments

“…Finally, DT binding sites also show some irregularities with respect to the proposed hypotheses . However, the regulation of DT binding sites is not particularly well understood at the current time, and previous studies looking at changes in DT sites in response to chronic DA agonist treatments have yielded highly conflicting results (Boulay et al, 1994;Vander Borght et al, 1995 ;Gordon et al, 1996) .…”

Chronic administration of the selective dopamine uptake inhibitor GBR 12909, but not cocaine, produces marked decreases in dopamine transporter density

“…GBR 12909 is thought to be longer acting than cocaine, and it is likely that some drug is still bound to the transporter 24 h after pump removal, although its dissociation rate from the dopamine transporter has not been reported. In a similar study, after twice daily injections (10 mg/kg/injection ×9 days) of GBR 12783, a compound that is structurally similar to GBR 12909, and is also a slow-dissociating compound (Bonnet et al 1986), there appeared to be negligible residual binding 48 h after the last injection as indicated by [ 3 H]mazindol binding to dopamine terminal regions including the striatum and nucleus accumbens (Boulay et al 1994). More compelling evidence that the decrease in binding is not merely due to residual bound drug, is that binding remains decreased to the same degree for at least four days in the caudate putamen, and 10 days in the nucleus accumbens.…”