Role of atypical opiates in OCD. Experimental approach through the study of 5-HT(2A/C) receptor-mediated behavior.
BACKGROUND
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.


OBJECTIVE
The aim of this study was to explore whether 5-HT2A-related behavior is affected by atypical opiate drugs.


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.
Rojas-Corrales
M Olga
MO
Group of Research and Development in Neuropsychopharmacology, Department of Neuroscience, Faculty of Medicine, University of Cádiz, Plz Falla 9, 11003, Cádiz, Spain.
Gibert-Rahola
Juan
J
Mico
Juan A
JA
D006916:5-Hydroxytryptophan; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003024:Clozapine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology; D007215:Indophenol / Q000031:analogs & derivatives; D007981:Levorphanol / Q000494:pharmacology; D008297:Male; D008691:Methadone / Q000494:pharmacology; D051379:Mice; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000502:physiology*; D044405:Receptor, Serotonin, 5-HT2C / Q000187:drug effects / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D020323:Tics / Q000503:physiopathology; D005879:Tourette Syndrome / Q000503:physiopathology*; D014147:Tramadol / Q000494:pharmacology; D014230:Triazoles / Q000494:pharmacology
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D010879:Piperazines; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D014230:Triazoles; C113896:dimethoxy-4-indophenyl-2-aminopropane; D007981:Levorphanol; D009270:Naloxone; D014147:Tramadol; D007215:Indophenol; C051752:nefazodone; D009020:Morphine; D006916:5-Hydroxytryptophan; D003024:Clozapine; D016666:Fluvoxamine; D003891:Desipramine; D008691:Methadone