Endogenous Dopamine (Da) Modulates [³H]spiperone Binding in Vivo in Rat Brain

Abstract

[3H]spiperone (SPI) binding in vivo, biochemical parameters and behavior were measured after modulating DA levels by various drug treatments. DA releasers and uptake inhibitors increased SPI binding in rat striatum. In other brain areas, the effects were variable, but only the pituitary remained unaffected. Surprisingly, nomifensine decreased SPI binding in frontal cortex. The effects of these drugs were monitored by measuring DA, serotonin (5-HT) and their metabolites in the same rats. The increased SPI binding in striatum was parallel to the locomotor stimulation with the following rank order: amfonelic acid greater than nomifensine greater than D-amphetamine greater than or equal to methylphenidate greater than amineptine greater than bupropion. Decreasing DA levels with reserpine or alpha-methyl-para-tyrosine reduced SPI binding by 45% in striatum only when both drugs were combined. In contrast, reserpine enhanced SPI binding in pituitary. Thus, the amount of releasable DA seems to modulate SPI binding characteristics. It is suggested that in vivo, DA receptors are submitted to dynamic regulation in response to changes in intrasynaptic concentrations of DA.

In Vivo Evidence for Dopamine-Mediated Internalization of D2-Receptors after Amphetamine: Differential Findings with [3H]Raclopride versus [3H]Spiperone

“…First, not all radioligands show this effect. Although benzamide radioligands (such as raclopride, IBZM, fallypride, clebopride) are always affected by endogenous DA in a manner consistent with the model (Innis et al, 1992;Volkow et al, 1994;Laruelle et al, 1995;Ginovart et al, 1997;Hartvig et al, 1997;Mach et al, 1997;Mukherjee et al, 1997), in vivo and ex vivo binding of butyrophenone compounds (such as spiperone, NMSP, pimozide) to D 2 -receptors show either no change or changes in the direction opposite that expected (Niehoff et al, 1979;Saelens et al, 1980;Bischoff et al, 1991;Onoe et al, 1994;Kobayashi et al, 1995). Second, the amphetamineinduced changes in […”

Anti-hyperactivity medication: methylphenidate and amphetamine

“…63 Paradoxically, however, short-term dextroamphetamine (from 5 min to 24 h before the radioligand) actually increased the binding of [ 3 H]spiperone to D2 receptors in animal brain striata. 61,[63][64][65][66][67][68][69] However, because D2 receptors can exist as monomers or dimers, with spiperone-like molecules preferring the monomer, 70 this apparently paradoxical rise in [ 3 H]spiperone binding to D2 receptors may reflect a rise in the density of D2 monomers following short-term exposure to dextroamphetamine. Altogether, although the dopamine D1 and D2 receptors are important components of the final path for controlling locomotor activity, there is at present no clear relation between the density of dopamine receptors and the immediate clinical action of the stimulants.…”

Effect of amphetamine-induced dopamine release on radiotracer binding to D1 and D2 receptors in rat brain striatal slices

“…These additional factors may be large enough to overcome the effect of competition with endogenous dopamine. For example, in rodent studies in which the binding of the high affinity D 2 radiotracer, [ 3 H]spiperone, was examined the striatal accumulation of this radiotracer has consistently been found to be increased rather than decreased by pharmacologically-induced increases in synaptic dopamine (Saelens et al 1980;Chugani et al 1988;Bischoff et al 1991).…”