Discriminative stimulus properties of the selective norepinephrine reuptake inhibitor, reboxetine, in rats.
BACKGROUND
Although drug discrimination procedures have proven difficult to apply to antidepressant agents, we recently characterized discriminative stimulus properties of the selective serotonin (5-HT) reuptake inhibitor, citalopram, in rats. However, discriminative stimulus properties of selective norepinephrine (NE) reuptake inhibitors remain to be evaluated.


OBJECTIVE
We determined the potential discriminative stimulus properties of the highly selective NE reuptake inhibitor and antidepressant, reboxetine.


METHODS
Employing a two-lever discrimination procedure, rats were trained to discriminate reboxetine (2.5 mg/kg, IP) from saline. In parallel, the influence of reboxetine (2.5 mg/kg) upon dialysate levels of monoamines in frontal cortex and dorsal hippocampus of freely moving rats was determined.


RESULTS
After 54+/-10 training sessions, reboxetine elicited robust stimulus recognition, fully generalizing to itself with an ED50 of 1.2 mg/kg. Two further NE reuptake inhibitors, desipramine (5.3) and maprotiline (1.8), as well as the 5-HT/NE reuptake inhibitor, venlafaxine (1.0), likewise generalized. In contrast, the 5-HT reuptake inhibitors, paroxetine, citalopram and sertraline, and the DA reuptake inhibitors, GBR12935 and bupropion, did not show significant generalization. Reboxetine markedly increased dialysate levels of NE, but not 5-HT, in frontal cortex and hippocampus. Dopamine (DA) levels were also (though less markedly) enhanced in frontal cortex.


CONCLUSIONS
In parallel with an elevation in extracellular levels of NE, the selective NE reuptake inhibitor, reboxetine, elicits a specific discriminative stimulus in rats.
Dekeyne
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Institut de Recherches Servier, Centre de Recherches de Croissy, Psychopharmacology Department, 125 Chemin de Ronde, 78290 Croissy-sur-Seine, Paris, France. anne.dekeyne@fr.netgrs.com
Gobert
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A
Iob
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Cistarelli
L
L
Melon
C
C
Millan
M J
MJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D004192:Discrimination, Psychological / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology*; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077593:Reboxetine; D012701:Serotonin / Q000378:metabolism
D018759:Adrenergic Uptake Inhibitors; D009025:Morpholines; D012701:Serotonin; D000077593:Reboxetine; D004298:Dopamine; D009638:Norepinephrine