The efficacy of reboxetine in preventing and reverting a condition of escape deficit in rats.
BACKGROUND
Different stress-induced experimental models of depression are currently used to study the efficacy and mechanism of action of classical or potential antidepressant compounds. We studied the effect of single and repeated administrations of reboxetine, an antidepressant that selectively inhibits noradrenaline reuptake, in the prevention and reversal of stress-induced escape deficit. Moreover, we examined the effect of chronic reboxetine on the stress-induced decrease of dopamine output in the nucleus accumbens shell (NAcS).


METHODS
Rats received a single or 21-day reboxetine administration before acute unavoidable stress exposure; 24 hours later their escape response was examined. Rats were exposed to repeated unavoidable stress for 21 days, with or without reboxetine treatment, and then were tested for escape; 2 days later they were implanted with microdialysis probes in the NAcS.


RESULTS
A single reboxetine administration showed a protective activity on stress-induced escape deficit development that significantly increased after 21 days of treatment. This effect was antagonized by propranolol, a selective beta-adrenergic antagonist. In rats exposed to chronic stress, a 21-day reboxetine treatment reinstated the avoidance response and NAcS dopamine output to control values.


CONCLUSIONS
In these stress-induced models, long-term reboxetine administration showed a protective activity similar to that of classical antidepressants.
Department of Neuroscience, Pharmacology Unit, University of Siena, Italy.
Silvia
S
Grappi
Giulio
G
Nanni
Benedetta
B
Leggio
Riccardo
R
Rauggi
Simona
S
Scheggi
Flavio
F
Masi
Carla
C
Gambarana
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004924:Escape Reaction / Q000187:drug effects*; D008124:Locomotion; D008297:Male; D017551:Microdialysis; D009025:Morpholines / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D013315:Stress, Psychological / Q000188:drug therapy* / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D009025:Morpholines; D000077593:Reboxetine; D004298:Dopamine