Effects of acute treatment with antidepressant drugs on sensorimotor gating deficits in rats.
BACKGROUND
Schizophrenic patients have a deficit in prepulse inhibition (PPI) which can be modelled in rats by administration of direct or indirect dopamine (DA) receptor agonists and N-methyl-D-aspartate (NMDA) receptor antagonists. Moreover, antipsychotics reverse the disruptive effect of DA agonists and NMDA receptor antagonists in this rat model. Consequently, this model is considered as predictive of antipsychotic action in the clinic. However, the effect of compounds, such as antidepressants, used for other psychiatric disorders but also administered to patients with schizophrenia has not been well investigated in this model. Antidepressants have been suggested not to affect PPI in humans. Thus, antidepressants are not expected to antagonise PPI disruption in rats, and should normally be used as negative controls in this model.


OBJECTIVE
To investigate the effects of three antidepressant compounds, a serotonin reuptake inhibitor, a dopamine reuptake inhibitor, and a noradrenaline reuptake inhibitor in the rat PPI model.


METHODS
The effect of acute treatment with citalopram, bupropion and desipramine on d-amphetamine-disrupted and phencyclidine (PCP)-disrupted PPI in rats was investigated. Ziprasidone was tested as a positive control.


RESULTS
None of the antidepressants, in contrast to ziprasidone, reversed PCP-disrupted PPI in rats. Both desipramine and ziprasidone normalised d-amphetamine-disrupted PPI, while citalopram and bupropion were inactive.


CONCLUSIONS
PCP-disrupted PPI in rats was less sensitive to false positives than the d-amphetamine-disrupted PPI model, based on the antidepressants tested in this study.
Pouzet
B
B
Department of Psychopharmacology, H. Lundbeck A/S, Ottiliavej 7, 2500, Valby, Denmark. brp@lundbeck.com
Andersen
M Paabøl
MP
Hogg
S
S
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000494:pharmacology; D016642:Bupropion / Q000008:administration & dosage / Q000494:pharmacology; D015283:Citalopram / Q000008:administration & dosage / Q000494:pharmacology; D003891:Desipramine / Q000008:administration & dosage / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology
D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D016642:Bupropion; D015283:Citalopram; D003891:Desipramine; D003913:Dextroamphetamine; D018765:Dopamine Uptake Inhibitors; D009638:Norepinephrine; D010879:Piperazines; D017367:Selective Serotonin Reuptake Inhibitors; D013844:Thiazoles; C092292:ziprasidone