Role of atypical opiates in OCD. Experimental approach through the study of 5-HT(2A/C) receptor-mediated behavior
by
Rojas-Corrales MO, Gibert-Rahola J, Mico JA.
Group of Research and Development in Neuropsychopharmacology,
Department of Neuroscience, Faculty of Medicine,
University of Cadiz, Plz Falla 9, 11003,
Cadiz, Spain,
juanantonio.mico@uca.es.
Psychopharmacology (Berl). 2006 Nov 11;


ABSTRACT

RATIONALE: The selective serotonin (5-HT) reuptake inhibitors (SSRIs) represent the first-line pharmacotherapy for obsessive-compulsive disorder (OCD), and atypical antipsychotic drugs, which block 5-HT2A receptors, are used in augmentation strategies. Opiate drugs are also effective in treatment-refractory OCD and Tourette syndrome. The 5-HT2A-related behavior (i.e., head twitch) has been related with tics, stereotypes, and compulsive symptoms observed in Tourette syndrome and OCD. OBJECTIVES: The aim of this study was to explore whether 5-HT2A-related behavior is affected by atypical opiate drugs. MATERIALS AND METHODS: Head-twitch response was induced in mice by administration of either 5-hydroxytryptophan (5-HTP) or the 5-HT2A/C agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI). Dose-effect curves of atypical opiate drugs [(+/-)-tramadol, (-)-methadone and levorphanol], morphine, and other psychoactive drugs (fluvoxamine, desipramine, nefazodone, and clozapine) were performed. Opioid mechanisms were investigated by administration of naloxone. RESULTS: All the opiates tested reduced both 5-HTP and DOI-induced behavior in a naloxone-reversible fashion, atypical opiates being more effective. The effects of the other drugs depended on the protocol, clozapine being the most effective. CONCLUSIONS: Combined 5-HT and opioid properties result in a greater efficacy in antagonizing 5-HT2A-related behavior. These results provide behavioral evidence to support convergent effects of the 5-HT and opioid systems in discrete brain areas, offering the potential for therapeutic advances in the management of refractory stereotypes and compulsive behaviors.
OCD
SSRIs
Sertraline
Fluoxetine
Citalopram
Paroxetine
Fluvoxamine
Clonazepam
OCD treatments
Compulsive disorders
SSRIs + clomipramine
St John's wort and OCD
Canine compulsive disorder
Drugs for treatment-resistant OCD
Venlafaxine versus paroxetine for OCD
Obsessive-Compulsive Disorder (OCD): mechanisms
OCD and selective serotonin reuptake inhibitors (SSRIs)


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