naloxone and Obsessive-Compulsive-Disorder

Topics: Adult; Arousal; Double-Blind Method; Female; Humans; Infusions, Intravenous; Male; Naloxone; Narcotic Antagonists; Obsessive-Compulsive Disorder; Opioid Peptides; Personality Inventory

Adrenocorticotropic hormone (ACTH) and cortisol secretion have been shown to be abnormal in approximately half of depressed patients. Information from pituitary and adrenal studies suggests that the locus of this dysregulation is at or above the level of the hypothalamus; however, direct evidence from provocative studies of the hypothalamic corticotropin releasing hormone (CRH) neuron does not exist. The current study was designed to stimulate hypothalamic CRH release using the opiate antagonist naloxone in patients with depression and elevated urinary-free cortisols as well as healthy and psychiatric controls. All subjects received naloxone and placebo on separate days in a double-blinded, randomized fashion at a dose determined previously to reliably induce significant increases in ACTH and cortisol secretion. No significant differences were noted among groups. We conclude that although naloxone is an effective central stimulant of the hypothalamic CRH neuron, stimulation of the hypothalamic CRH neuron with naloxone does not provide evidence of dysregulation of the HPA axis in depression.

Topics: Adrenocorticotropic Hormone; Adult; Behavior; Depressive Disorder; Double-Blind Method; Female; Humans; Hydrocortisone; Male; Naloxone; Narcotic Antagonists; Obsessive-Compulsive Disorder; Pituitary-Adrenal System; Stimulation, Chemical

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

Topics: 5-Hydroxytryptophan; Analgesics, Opioid; Animals; Clozapine; Desipramine; Disease Models, Animal; Dose-Response Relationship, Drug; Fluvoxamine; Indophenol; Levorphanol; Male; Methadone; Mice; Morphine; Naloxone; Narcotic Antagonists; Obsessive-Compulsive Disorder; Piperazines; Receptor, Serotonin, 5-HT2A; Receptor, Serotonin, 5-HT2C; Stereotyped Behavior; Tics; Tourette Syndrome; Tramadol; Triazoles

Two patients with obsessive-compulsive disorder experienced an exacerbation of chronic obsessional doubt after double-blind, placebo-controlled administration of naloxone. Endogenous opiates may be involved in the pathogenesis of this symptom.

Topics: Acute Disease; Adult; Double-Blind Method; Endorphins; Humans; Male; Middle Aged; Naloxone; Obsessive-Compulsive Disorder