Abstract | RATIONALE: The combination of idazoxan, a specific alpha(2)-adrenoceptor antagonist with raclopride, a selective D(2)/D(3) receptor antagonist, has been recently proposed to produce an "atypical" antipsychotic profile comparable to that of clozapine, based on an animal study which analysed dopamine efflux in the medial prefrontal cortex and the preclinical test of conditioned avoidance response (CAR) for evaluation of antipsychotic potential. Accordingly, the combination of a "typical" antipsychotic with idazoxan has been proposed as an augmentation strategy in treatment-resistant schizophrenia, although its therapeutic potential remains difficult to predict. OBJECTIVES: Given the momentum stimulated by these reports, the present study investigated whether the combination of idazoxan with raclopride is indeed sufficient to mimic the ability of clozapine to reverse prepulse inhibition (PPI) deficits in rats, a behavioral paradigm that models PPI deficits observed in the schizophrenia spectrum, and currently the only test which reliably appears to distinguish between "typical" antipsychotics and compounds with "atypical" antipsychotic potential. METHODS: RESULTS: CONCLUSION: The present results challenge the hypothesis that simple alpha(2)/D(2) blockade is sufficient to produce clozapine-like "atypical" antipsychotic activities, and support the consensus that the PPI paradigm represents the most sophisticated behavioral preclinical test for detecting selective "atypical" profile of antipsychotics.
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Authors | M Ballmaier, M Zoli, R Mazzoncini, M Gennarelli, F Spano |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 159
Issue 1
Pg. 105-10
(Dec 2001)
ISSN: 0033-3158 [Print] Germany |
PMID | 11797077
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Adrenergic alpha-2 Receptor Antagonists
- Antipsychotic Agents
- Dopamine D2 Receptor Antagonists
- Hallucinogens
- Receptors, Adrenergic, alpha-2
- Receptors, Dopamine D2
- Phencyclidine
- Clozapine
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Topics |
- Adrenergic alpha-2 Receptor Antagonists
- Animals
- Antipsychotic Agents
(pharmacology)
- Clozapine
(pharmacology)
- Dopamine D2 Receptor Antagonists
- Dose-Response Relationship, Drug
- Hallucinogens
(pharmacology)
- Male
- Phencyclidine
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Receptors, Adrenergic, alpha-2
(physiology)
- Receptors, Dopamine D2
(physiology)
- Reflex, Startle
(drug effects, physiology)
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