Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats

Abstract

In parallel with an elevation in extracellular levels of NE, the selective NE reuptake inhibitor, reboxetine, elicits a specific discriminative stimulus in rats.

Differential modulation of efficiency in a food-rewarded "differential reinforcement of low-rate" 72-s schedule in rats by norepinephrine and serotonin reuptake inhibitors

“…Irrespective of the underlying receptorial and "psychological" mechanisms, the reproducible actions of NARIs in DRL 72-s procedures complements observations of their activity in diverse experimental models predictive of antidepressant properties (Detke et al 1995;Wong et al 2000;Dekeyne et al 2001;Millan et al 2001b) and their clinical utility in the management of depressive states (Frazer 1997;Massana et al 1999;Schatzberg 2000).…”

“…Venlafaxine displays robust effects in virtually all preclinical models predictive of antidepressant properties, is active in experimental protocols of impulsive behaviour (Schweizer et al 1997;Redrobe et al 1998;Millan et al 2001a) and generalises to discriminative stimuli elicited by the NARI reboxetine and the SSRI citalopram (Millan et al 2001a;Dekeyne et al 2001). Its lack of activity in role of NE transporters in this structure on the reuptake of DA (Millan et al 2000b).…”

“…Further, only few experimental models of antidepressant properties have succeeded in differentiating SSRIs and NARIs (Detke et al 1995;Dekeyne et al 2001;Millan et al 2001a). Nevertheless, it is important to address the question as to why SSRIs were ineffective.…”

Effects of Antidepressants in Rats Trained to Discriminate Centrally Administered Isoproterenol

“…Bupropion has been reported to inhibit norepinephrine uptake and down-regulate ␤-adrenergic receptors (Gandolfi et al, 1983;Alhaider and Mustafa, 1988;Ascher et al, 1995); however, there are a number of contradictory reports (Bryant et al, 1983;Ferris and Beaman, 1983;Suranyi-Cadotte et al, 1995). In rats trained to discriminate the norepinephrine uptake inhibitor reboxetine from vehicle, doses of 2.5 and 10 mg/kg bupropion did not substitute (Dekeyne et al, 2001). In contrast, other norepinephrine uptake inhibitors did substitute for reboxetine.…”

Discriminative stimulus properties of the “atypical” antidepressant, mirtazapine, in rats: a pharmacological characterization

“…This is unfortunate since discriminative stimulus (DS) studies are potentially instructive in evaluating several interesting issues: first, in determining whether a training drug shares interoceptive effects with other classes of clinically active antidepressant; second, in characterizing mechanisms of action involved in the interoceptive effects of antidepressants using substitution tests with ligands selective for specific classes of receptor and transporter; third, in relating DS properties of antidepressants to their functional actions, including their influence upon mood. In fact, despite difficulties faced in training, these questions have been addressed in drug discrimination studies of the selective serotonin (5-HT) reuptake inhibitor (SSRI), citalopram, the selective noradrenaline (NA) reuptake inhibitor (NARI), reboxetine, and dopamine (DA) reuptake inhibitor, bupropion (Olivier et al 1993;Terry and Katz 1997;Millan et al 1999aMillan et al , 1999bDekeyne et al 2001aDekeyne et al , 2001bYoung and Glennon 2002;Millan and Dekeyne 2007; see Dekeyne and Millan 2003 for review). By contrast, the poor tolerance of tricyclic agents upon longterm administration, has complicated their use as training drugs (Zhang and Barrett 1991;Dekeyne and Millan 2003).…”