Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxytocin (OXT), a neurohypophyseal hormone, has a wide range of behavioral effects outside its classic peripheral endocrine functions. OXT involvement in adaptive central nervous system processes has been demonstrated as an inhibitory, amnestic action on learning and memory in different paradigms. Because adaptation and learning are likely to be involved in the neural events leading to drug tolerance and dependence, the question logically arose whether OXT is able to influence the development of tolerance of and dependence on abused drugs. In this review, we summarize our results on the effects of OXT on opiate (including morphine, heroin, and the endogenous opiates beta-endorphin and enkephalin) tolerance and dependence, heroin self-administration, psychostimulant-induced behavioral changes, and behavioral tolerance and sensitization. The sites and mechanisms of action and the possible physiological role of OXT are also discussed. In the first part of this review the effects of exogenously administered OXT on both the acute and chronic behavioral effects of opiates and psychostimulants have been summarized. OXT inhibited the development of tolerance to morphine, heroin, beta-endorphin, and enkephalin, OXT also inhibited the development of cross-tolerance between the predominantly mu-agonist heroin and the predominantly delta-agonist enkephalin in mice. Naloxone-precipitated morphine withdrawal syndrome was also attenuated by OXT. Heroin self-administration was decreased by OXT administration in heroin-tolerant rats. OXT inhibited cocaine-induced exploratory activity, locomotor hyperactivity, and stereotyped behavior in rats and in mice. Behavioral tolerance to cocaine was also attenuated by OXT. On the contrary, OXT stimulated the development of behavioral sensitization to cocaine. OXT did not alter the stereotyped behavior induced by amphetamine. In the second series of experiments, the sites of action of OXT on drug-related behavior were investigated. Intracerebro-ventricular (ICV) and intracerebral (IC) administration of an OXT-receptor antagonist inhibited the effects of peripherally administered OXT on morphine tolerance, heroin self-administration, and cocaine-induced sniffing behavior. This suggests the central, intracerebral location of OXT target sites. Local IC microinjection of OXT in physiological doses into the posterior olfactory nucleus, tuberculum olfactorium, nucleus accumbens, central amygdaloid nucleus, and the hippocampus inhibited the development of tolerance to and dependence on morphine as well as cocaine-induced sniffing behavior and tolerance to cocaine. The physiological role of endogenous OXT in acute morphine tolerance has also been demonstrated, since OXT antiserum (ICV) and OXT-receptor antagonist (injected into the basal forebrain structures) potentiated the development of morphine tolerance. Finally, we investigated the possible mechanisms of action of OXT on drug related behavior. Both morphine tolerance and dependence, and cocaine administration, increased dopamine utilization in the mesencephalon and in the nucleus accumbens, respectively. OXT treatment decreased the alpha-methylparatyrosine-induced dopamine utilization in the mesencephalon and in the nucleus accumbens-septal complex. Chronic OXT treatment decreased the number of apparent binding sites of dopamine in the basal forebrain area. It also inhibited a cocaine-induced increase in dopamine utilization in the nucleus accumbens, but not in the striatum. In light of this information, it appears that OXT inhibits the development of opiate tolerance, dependence, and self-administration as well as the acute behavioral actions of and chronic tolerance to cocaine. This suggests the possible role of this neuropeptide in the regulation of drug abuse. Therefore, OXT may act as a neuromodulator on dopaminergic neurotransmission in limbic-basal forebrain structures to regulate adaptive CNS processes leading to drug addiction.
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PMID:Role of oxytocin in the neuroadaptation to drugs of abuse. 921 Feb 15

A disruption of the oxytocin system seems to affect a variety of brain functions including emotions, mood and social behavior possibly underlying severe social deficits and susceptibility for substance use and mental health disorders. Early life adversity, such as insecure attachment in childhood, has been suggested to influence oxytocin tone contributing to a condition of neurobiological vulnerability. Aim of the present study was to investigate oxytocin serum levels in abstinent heroin addicted patients, in comparison with healthy controls, and the possible correlation with co-occurring psychiatric symptoms, aggressiveness and perception of parental neglect. Eighteen (18) abstinent patients, affected by heroin use disorders, and 18 control subjects, who never used drugs or abused alcohol, were included in the study and submitted to 1) collection of a blood sample for oxytocin assay, 2) Symptoms Check List 90 for psychiatric symptoms evaluation 3) Buss Durkee Hostility Inventory to measure aggressiveness 4) Child Experience of Care and Abuse-Questionnaire to retrospectively test the perception of parental neglect. Heroin exposure extent and heroin dosages were also recorded. Oxytocin serum levels were unexpectedly significantly higher among abstinent patients affected by heroin use disorders and positively correlated with psychiatric symptoms, aggressiveness and mother neglect scores. No correlation was evidenced between oxytocin and heroin exposure extent or dosages. Our findings appear to contradict the simplistic view of oxytocin as a pro-social hormone and confirm previous evidence concerning the peptide levels direct association with aggressive behavior and mood disorders. Considering a more complex mechanism, oxytocin would increase the sensitivity to social salience cues related to contextual or inter-individual factors, promoting pro-sociality in "safe" conditions and, in contrast, inducing more defensive and "anti-social" emotions and behaviors when the social cues are interpreted as "unsafe". This latter condition is often characterizing the clinical history of addicted patients.
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PMID:Increased oxytocin levels among abstinent heroin addicts: Association with aggressiveness, psychiatric symptoms and perceived childhood neglect. 2809 20