heroin and phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide

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

Neuropeptide FF (NPFF) is a mammalian FMRFamide-like octapeptide with antiopioid properties that inhibits morphine-induced analgesia but also produces hyperalgesia. In the present study, a series of three experiments was carried out to investigate the interactions between opioid receptor stimulation and antiopioid systems. First, by using in vitro superfusion system with rat spinal cord slices, we showed that morphine stimulated NPFF release in a dose-dependent manner. The stimulating effect which was observed with morphine concentrations as low as 100 fM reached a maximum at 0.1 nM, then decreased and was ineffective at 10 microM. The morphine-induced release of NPFF was abolished by naloxone (1 microM) but unaltered by tetrodotoxin. Second, by an in vivo approach, we showed that a single heroin administration (2.5 mg/kg, s.c.) elicited in 30 min a drastic drop (38%) in spinal NPFF content. In a third experiment, we evaluated the capacity of naloxone in revealing an antiopioid component associated with opioid receptor stimulation. The administration of naloxone (1 mg/kg, s.c..) 25 min following that of heroin (2.5 mg/kg, s.c.) not only abolished the heroin-induced increase of tail-flick latency, but also lowered it under the basal value by 30%. These results indicate that opioid receptor stimulation activates both pain inhibitory and pain facilitatory systems in which NPFF may play a significant role and that opiate-induced analgesia is always partly masked.

Topics: Animals; Heroin; In Vitro Techniques; Male; Morphine; Naloxone; Narcotic Antagonists; Neuropeptides; Oligopeptides; Pain; Rats; Rats, Sprague-Dawley; Reaction Time; Receptors, Opioid; Spinal Cord; Tetrodotoxin