neuropeptide-y and Heroin-Dependence

To examine the effects of Han's acupoint and nerve stimulator (HANS) electroacupuncture on the expression of NPY in periaqueductal grey (PAG) of heroin addicted rats.. Heroin was injected subcutaneously according to the principle of daily increasing dose in rats of experimented group. The ability of special learning and memory were tested by Morris water maze; The expression of NPY in PAG of rat were detected by immunohistochemistry.. (1) Escape latency and searching distance in heroin-addiction group were significantly increased compared with those of normal group during the place navigation test (P < 0.05). However, in acupuncture group, escape latency and searching distance was obviously shortened compared with those of heroin-addiction group (P < 0.05). The exploring time and distance of original platform area in proportion to the total distance in heroin-addiction group significantly decreased compared with those of normal group during spatial probe test (P < 0.05). The exploring time and distance of original platform area in proportion to the total distance in acupuncture group was increased compared with those in heroin-addiction group (P < 0.01). (2) The expression of NPY of heroin-addiction group was lower than that in normal group in PAG, while those of acupuncture group was higher than that in the heroin-addiction group (P < 0.05).. The learning and memory induced by heroin-addiction could be reversed and the expression of NPY in PAG was increased by HANS in rats.

Topics: Animals; Electroacupuncture; Heroin Dependence; Male; Maze Learning; Memory; Neuropeptide Y; Periaqueductal Gray; Rats; Rats, Wistar

Previous studies have shown that individuals withdrawn from chronic opiate administration undergo substantial elevations of cortisol levels with blunted corticotropin (ACTH) rhythms and that these changes persist beyond the 7-10 days of acute withdrawal symptoms. However, there are no published studies of changes in expression of clock genes or of other neuropeptides related to circadian-rhythm regulation, which may influence relapse susceptibility.. Blood samples were collected from 8 healthy control subjects and 16 heroin addicts during pharmacologically unassisted withdrawal on the 3rd, 10th, and 30th days of abstinence at 3-hour intervals for 24 hours. Outcome measures were the relative expression of clock gene mRNA (hperiod1, hperiod2, hclock) and the levels of serum cortisol, plasma ACTH, beta-endorphin (beta-EP), leptin, neuropeptide Y, interleukin-2 (IL-2), and tumor necrosis factor (TNF) in these subjects.. Compared with healthy volunteers, abstinent addicts showed disruptions in diurnal rhythms of hPER1 and hPER2 mRNA expression, along with disruptions in diurnal rhythms of cortisol, ACTH, beta-endorphin, leptin, and IL-2 release. Several of these disruptions (hPER1, hPER2, ACTH, beta-endorphin, and IL-2) persisted for the 30-day testing period, as did elevation of 24-hour levels of cortisol and decreases in 24-hour IL-2 and TNF levels.. These prolonged neurobiological changes may play a role in protracted opiate withdrawal symptoms and contribute to relapse vulnerability.

Topics: Adrenocorticotropic Hormone; Adult; Animals; beta-Endorphin; Case-Control Studies; Chronobiology Disorders; CLOCK Proteins; Drug Users; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); Heroin Dependence; Humans; Hydrocortisone; Hypothalamus; Interleukin-2; Intracellular Signaling Peptides and Proteins; Leptin; Male; Neuropeptide Y; Nuclear Proteins; Period Circadian Proteins; Rats; RNA; Substance Withdrawal Syndrome; Time Factors; Trans-Activators; Transcription Factors; Tumor Necrosis Factor-alpha

Heroin use and withdrawal cause abnormality in the endocrine system. However, the time course of neuroendocrine alterations in heroin addicts during pharmacologically unassisted withdrawal is still unclear.. To investigate alterations in cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin (beta-EP), leptin, and neuropeptide Y (NPY) during the first month of abstinence in heroin addicts.. Twelve heroin addicts and eight matched healthy control subjects were recruited for this study. The neuroendocrine alterations and self-reported heroin craving, anxiety, and depression in heroin addicts were assessed at different time points (days 3, 10, and 30) of first month of abstinence from heroin use.. Self-reported heroin craving, anxiety, and depression in heroin addicts decreased gradually during the first month of abstinence. The cortisol levels increased from abstinence day 3 to 30, while ACTH and beta-EP levels decreased over this period in heroin addicts. The leptin and NPY levels were significantly decreased on days 3 and 10 but had normalized on day 30 of abstinence. A positive correlation between cortisol level and heroin craving, anxiety, and depression was observed, while a negative correlation was observed between beta-EP level and craving and anxiety and between leptin and depression and NPY and anxiety.. Abnormal alterations in the neuroendocrine system, including levels of cortisol, ACTH and beta-EP persist throughout the first month of abstinence. These results suggest that neuroendocrine system dysfunctions in heroin abusers is independent of the acute and protracted withdrawal syndromes, and may thus contribute to relapse to heroin use.

Topics: Adrenocorticotropic Hormone; Adult; Analysis of Variance; Anxiety; beta-Endorphin; Case-Control Studies; Depression; Heroin; Heroin Dependence; Humans; Hydrocortisone; Leptin; Male; Neuropeptide Y; Neurosecretory Systems; Patient Selection; Psychiatric Status Rating Scales; Radioimmunoassay; Substance Withdrawal Syndrome; Time Factors

Numerous findings suggest that drug seeking and ingestive behaviors share common neurobiological mechanisms, but the relevant pathways are unknown. Dietary manipulations result in changes in endocrine the and/or neuropeptide signals, such as the hormones leptin and ghrelin, which are dynamically linked to energy balance and the regulation of feeding behavior. We have recently demonstrated that food deprivation-induced reinstatement of heroin seeking can be blocked with leptin, and others have suggested a role for ghrelin in drug-related behaviors. The feeding-relevant effects of leptin and ghrelin involve the inhibition or activation, respectively, of neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus. However, the effects of NPY, a highly potent orexigenic peptide, on drug-related behaviors have not been thoroughly studied. Here we examined the effect of acute NPY administration on the rate of heroin self-administration and the reinstatement of extinguished heroin-seeking behavior. Heroin intake (0.05mg/kg/infusion) was tested using a self-administration procedure (FR-1), 10-min post-NPY injections (0.0, 4.0, and 10microg/rat, ICV). In a different group of rats, NPY-induced reinstatement (0.0, 4.0, and 10microg/rat, ICV) of extinguished heroin seeking was assessed. NPY injections increased on-going heroin self-administration, and induced a reinstatement of extinguished heroin-seeking behavior. These findings suggest that NPY can modulate the rewarding and conditioned reinforcing effects of drugs of abuse.

Topics: Animals; Behavior, Animal; Conditioning, Operant; Disease Models, Animal; Food Deprivation; Heroin; Heroin Dependence; Male; Narcotics; Neuropeptide Y; Rats; Rats, Long-Evans; Reinforcement Schedule; Reinforcement, Psychology; Self Administration

Immunohistochemical distribution patterns of neuropeptide FF (NPFF) and neuropeptide tyrosine (NPY) were studied in the brain of rats submitted to two different protocols of heroin treatment. In drug-naive rats, acutely injected heroin significantly depleted NPFF-immunoreactive material within the neurons of the nucleus of solitary tract (NTS), significantly decreased the density of NPFF-immunoreactive nerve fibers within the median eminence, pituitary stalk, and neurohypophysis, and markedly increased NPY-immunoreactive neurons and nerve fibers in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. In drug-sensitized rats, heroin significantly increased the number and immunostaining intensity of the NPFF-immunoreactive neurons within the NTS and induced minor changes in the NPFF-immunoreactive nerve fiber network of the median eminence, pituitary stalk, and neurohypophysis and a relatively minor increase in NPY neurons in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. These heroin-induced changes suggest that NPFF is involved in regulating the effects of the heroin injection and in the mechanisms underlying behavioral sensitization. They also add further support to the key role of NPY in any conditions tending to change the animal homeostasis.

Topics: Animals; Brain; Brain Chemistry; Disease Models, Animal; Heroin; Heroin Dependence; Hypothalamo-Hypophyseal System; Immunohistochemistry; Male; Midline Thalamic Nuclei; Narcotics; Neuropeptide Y; Oligopeptides; Pituitary Gland; Presynaptic Terminals; Rats; Rats, Sprague-Dawley; Septal Nuclei; Solitary Nucleus