Regulation of Dopamine Receptors by Bupropion: Comparison with Antidepressants and CNS Stimulants

Abstract

Acute treatment of rats with the antidepressant bupropion increased [3H]spiperone binding to D2 receptors in vivo. This dose- and time-dependent effect was greatest in striatum and minimal in cerebellum and pituitary. A parallel behavioral stimulation occurred in the same rats. Among 21 antidepressants and CNS stimulants tested, only those that activate dopamine (DA) transmission had similar effects: nomifensine, amineptine, methylphenidate, D-amphetamine, amfonelic acid, cocaine, benztropine and GBR 12909. Decreasing DA transmission with reserpine plus alpha-methyl-p-tyrosine prevented the action of bupropion. Finally, bupropion was inactive in vitro and ex-vivo. Therefore, we propose that bupropion and other DA-enhancing agents modify the characteristics of [3H]spiperone binding through the intervention of a dynamic regulation of the D2 receptors by the neurotransmitter itself.

Catecholamine Reuptake Inhibition Causes Weight Loss by Increasing Locomotor Activity and Thermogenesis

“…Acute and chronically administered BUP has repeatedly been demonstrated to dose dependently increase locomotor activity in rodents with similar potency, regardless of species, age, or strain (Soroko et al, 1977;Nielsen et al, 1986;Zarrindast and Hosseini-Nia, 1988;Vassout et al, 1993;Redolat et al, 2005;Mitchell et al, 2006;Billes and Cowley, 2007). The current finding that BUP, DA, and DA + NE reuptake inhibition all transiently increased locomotor activity is consistent with the idea that inhibition of the DA transporter is sufficient to cause a significant short-term increase in locomotion and even reverse the decrease in activity caused by inhibition of NE reuptake.…”

“…The transient increase in locomotor activity caused by subchronic BUP infusion is identical to the effect caused by subchronic infusion of various selective DA reuptake inhibitors (Izenwasser et al, 1999). A dopaminergic mechanism for increased locomotor activity by BUP is consistent with increased striatal DA concentrations in rats following acute BUP administration (Vassout et al, 1993), the failure of BUP to increase locomotor activity in rats with selective ablation of DA neurons (Cooper et al, 1980), and a recent report by Mitchell et al (2006) demonstrating that acute BUP Figure 6 Effect of subchronic DA and NE reuptake inhibition on daily body weight and food intake. Adult mice received subchronic infusion of either nisoxetine (NIS, 1.5 mg/kg/h), GBR12783 (GBR, 2.5 mg/kg/h), NIS (1.5 mg/kg/h) + GBR (2.5 mg/kg/h), or vehicle.…”

“…Because reports on the acute effects of BUP on temperature are inconsistent, further research is needed to determine if increased thermogenesis might also contribute to increased energy expenditure by BUP (Zarrindast and Abolfathi-Araghi, 1992;Liu et al, 2002;Hasegawa et al, 2005). We and others have shown that acute peripheral BUP also dose dependently stimulates locomotor activity in rodents, an effect that is consistent with inhibition of the DA transporter (Soroko et al, 1977;Cooper et al, 1980;Nielsen et al, 1986;Zarrindast and Hosseini-Nia, 1988;Vassout et al, 1993;Redolat et al, 2005;Mitchell et al, 2006).…”

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.…”

Bupropion Sustained Release Treatment Reduces Fatigue in Cancer Patients

“…Psychopharmacologically, it shares a wide range of actions with psychostimulants. The mode of action is believed to involve primarily dopaminergic and noradrenergic rather than serotonergic mechanisms (24)(25)(26). The safety of bupropion in humans has been extensively studied (27)(28)(29).…”