enkephalin-leu--ala(2)-cys(6)- and naltrindole

Intake of a palatable sucrose solution in real-fed rats is mediated in part by central mu and kappa opioid receptors. Since general opioid antagonists still inhibit sucrose intake in sham-fed rats, the present study examined whether centrally administered mu (beta-funaltrexamine: 5, 20 micrograms), mu1 (naloxonazine: 50 micrograms), kappa (nor-binaltorphamine: 1, 5, 20 micrograms), delta (naltrindole: 20 micrograms) or delta 1 (DALCE: 40 micrograms) opioid subtype antagonists altered sucrose intake in sham-fed rats in a similar manner to systemic naltrexone (0.01-1 mg/kg) and whether such effects were equivalent to altering the sucrose concentration. Sucrose (20%) intake in sham-fed rats was significantly and dose-dependently reduced by naltrexone (59%), beta-funaltrexamine (44%) and nor-binaltorphamine (62%), but not by naloxonazine, naltrindole or DALCE. The reductions in sham sucrose (20%) intake by general, mu and kappa antagonism were similar in pattern and magnitude to diluting sucrose concentration from 20% to 10% in untreated sham-fed rats. Since both real-fed and sham-fed rats share similar patterns of specificity of opioid effects, magnitudes and potencies of inhibition, it suggests that central mu and kappa antagonism acts on orosensory mechanisms supporting sucrose intake.

Topics: Animals; Cerebral Ventricles; Eating; Enkephalin, Leucine-2-Alanine; Infusions, Parenteral; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Sucrose

Intake of either hypotonic or hypertonic saline solutions is modulated in part by the endogenous opioid system. Morphine and selective mu and delta opioid agonists increase saline intake, while general opioid antagonists reduce saline intake in rats. The present study evaluated whether intracerebroventricular administration of general (naltrexone) and selective mu (beta-funaltrexamine, 5-20 micrograms), mu, (naloxonazine, 50 micrograms), kappa (nor-binaltorphamine, 5-20 micrograms), delta (naltrindole, 20 micrograms), or delta 1 (DALCE, 40 micrograms) opioid receptor subtype antagonists altered water intake and either hypotonic (0.6%) or hypertonic (1.7%) saline intake in water-deprived (24 h) rats over a 3-h time course in a two-bottle choice test. Whereas peripheral naltrexone (0.5-2.5 mg/kg) significantly reduced water intake and hypertonic saline intake, central naltrexone (1-50 micrograms) significantly reduced water intake and hypotonic saline intake. Water intake was significantly reduced following mu and kappa receptor antagonism, but not following mu 1, delta, or delta 1 receptor antagonism. In contrast, neither hypotonic nor hypertonic saline intake was significantly altered by any selective antagonist. These data are discussed in terms of opioid receptor subtype control over saline intake relative to the animal's hydrational state and the roles of palatability and/or salt appetite.

Topics: Animals; Enkephalin, Leucine-2-Alanine; Hypotonic Solutions; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Saline Solution, Hypertonic; Water Deprivation

Opioid modulation of ingestion includes general opioid antagonism of different forms of water intake, mu 2 receptor modulation of deprivation-induced water intake and delta 2 receptor modulation of saccharin intake. Water intake is stimulated by both central administration of angiotensin II (ANG II) and peripheral administration of a hypertonic saline solution; both responses are reduced by general opioid antagonists. The present study examined whether specific opioid receptor subtype antagonists would selectively alter each form of water intake in rats. Whereas systemic naltrexone (0.1-2.5 mg/kg, s.c.) reduced water intake induced by either peripheral ANGII (500 micrograms/kg, s.c.) or hypertonic saline (3 ml/kg, 10%), intracerebroventricular (i.c.v.) naltrexone (1-50 micrograms) only inhibited central ANGII (20 ng)-induced hyperdipsia. Both forms of drinking were significantly and dose-dependently inhibited by the selective kappa antagonist, nor-binaltorphamine (Nor-BNI, 1-20 micrograms). Whereas both forms of drinking were transiently reduced by the mu-selective antagonist, beta-funaltrexamine (beta-FNA, 1-20 micrograms), the mu 1 antagonist, naloxonazine (40 micrograms) stimulated drinking following hypertonic saline. The delta 1 antagonist, [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, 1-40 micrograms) significantly reduced drinking following ANGII, but not following hypertonic saline; the delta antagonist, naltrindole failed to exert significant effects. These data indicate that whereas kappa opioid binding sites modulate hyperdipsia following hypertonic saline, mu 2, delta 1, and kappa opioid binding sites modulate hyperdipsia following ANGII. The mu 1 opioid binding site may normally act to inhibit drinking following saline.

Topics: Angiotensin II; Animals; Drinking; Enkephalin, Leucine-2-Alanine; Male; Naltrexone; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, mu; Saline Solution, Hypertonic

Naloxone and naltrindole attenuate the locomotor response to amphetamine, implicating delta-opioid receptors in the opioid-antagonist/amphetamine interaction. To determine the role of delta-opioid receptor subtypes in this phenomenon, rats were pretreated with the following selective antagonists administered intracisternally: naltrindole, [D-Ala2,Leu5,Cys6]enkephalin (DALCE, delta 1 receptor selective), naltrindole-5'-isothiocyanate (delta 2 receptor selective). Cumulative dose-response curves to amphetamine were constructed (saline, 0.1, 0.4, 1.6 and 6.4 mg/kg s.c.), with injections every 30 min. Naltrindole was also tested against cumulative doses of cocaine (saline, 3.0, 10, 30 and 56 mg/kg i.p.). Gross and fine motor activity were recorded for 20 min, commencing 10 min postinjection. Amphetamine and cocaine dose dependently increased both gross and fine movements. Naltrindole (10 micrograms) attenuated the gross but not fine activity response to amphetamine, but 10 or 30 micrograms failed to influence the response to cocaine. Naltrindole-5'-isothiocyanate (30 micrograms) attenuated slightly but significantly the gross activity response to amphetamine, whereas DALCE (30 micrograms) was without effect. However, a combination of 10 micrograms each of DALCE and naltrindole-5'-isothiocyanate markedly attenuated the amphetamine-induced increases in gross movements without altering fine activity. These data provide further evidence for the involvement of delta-opioid receptors in the modulation of behavioral effects of amphetamine; both delta 1- and delta 2-opioid receptors appear to play a role. The differential effects of opioid antagonists on locomotor activity stimulated by amphetamine and cocaine suggests differences in the mechanism of action of these drugs not previously appreciated.

Topics: Amphetamine; Animals; Cocaine; Dose-Response Relationship, Drug; Enkephalin, Leucine-2-Alanine; Male; Motor Activity; Naloxone; Naltrexone; Narcotic Antagonists; Rats; Rats, Sprague-Dawley; Receptors, Opioid, delta

Tail-pinch feeding (TPF) in rats is decreased following general (naltrexone, NTX) and mu (Cys2-Tyr3-Orn5-Pen7-amide, CTOP) opioid antagonists, but not following kappa (nor-binaltorphamine. Nor-BNI) or delta (naltrindole, NTI) opioid antagonists. Because multiple mu (mu1 and mu2) and delta (delta 1 and delta 2) opioid receptor subtypes have been characterized, the present study evaluated whether TPF was differentially altered following ICV administration of general (NTX), mu (beta-funaltrexamine, B-FNA), mu1 (naloxonazine, NAZ), kappa (Nor-BNI), delta 1 ([D-Ala2, Leu5, Cys6]-enkephalin, DALCE) and delta 2 (NTI) opioid antagonists. Like the reversible mu antagonist CTOP, the irreversible mu antagonist B-FNA significantly and dose-dependently (1-20 micrograms) reduced TPF by up to 28%. In contrast, whereas NAZ (50 micrograms) reduced TPF by 32%, this effect was highly variable and failed to achieve significance. Neither NTX (5-10 mg/kg, SC), Nor-BNI (20 micrograms), DALCE (40 micrograms) nor NTI (20 micrograms) significantly altered TPF, suggesting that kappa, delta 1 and delta 2 opioid receptor subtypes were not involved. Because no antagonist altered the duration of food contact during tail pinch, it appears that the opioid effect modulates ingestive rather than activational mechanisms. The reliable inhibition of TPF by B-FNA (mu1 and mu2), together with the variable effect of naloxonazine (mu1), appears to implicate both mu binding sites in this response.

Topics: Animals; Arousal; Enkephalin, Leucine-2-Alanine; Feeding Behavior; Indoles; Male; Morphinans; Naloxone; Naltrexone; Narcotic Antagonists; Nociceptors; Rats; Rats, Sprague-Dawley; Receptors, Opioid, mu

Opioid modulation of ingestion includes general opioid antagonism of deprivation-induced water intake and intake of sucrose and saccharin solutions. Previous studies using selective subtype antagonists indicated that opioid effects upon deprivation-induced water intake occurred through the mu2 receptor and that opioid effects upon sucrose intake occurred through kappa and mu2 receptors. The present study compared the effects of intracerebroventricular administration of opioid receptor subtype antagonists upon intakes of a saccharin solution and a maltose dextrin (MD) solution to determine which receptor subtypes were involved in modulation of ingestion of different preferred tastants. Significant reductions in saccharin intake (1 h) occurred following naltrexone (20-50 micrograms: 66%) and naltrindole (delta, 20 micrograms: 75%), whereas [D-Ala2, Leu5, Cys6]-enkephalin (DALCE, delta 1, 40 micrograms: 45%) had transient (5 min) effects. Neither beta-funaltrexamine (B-FNA, mu), naloxonazine (mu1), nor nor-binaltorphamine (Nor-BNI, kappa) significantly altered saccharin intake. Significant reductions in MD intake (1 h) occurred following naltrexone (5-50 micrograms: 69%) and B-FNA (1-20 micrograms: 38%). MD intake was not reduced by naltrindole, DALCE, naloxonazine and Nor-BNI. Peak antagonist effects were delayed (20-25 min) to reflect interference with the maintenance, rather than the initiation of saccharin or MD intake. Comparisons of opioid antagonist effects across intake situations revealed that naltrexone had consistently low ID40 values for saccharin (29 nmol), MD (25 nmol), sucrose (6 nmol) and deprivation (38 nmol) intake. Despite its significant effects relative to naloxonazine, B-FNA had significantly higher ID40 values for saccharin (800 nmol), MD (763 nmol) and sucrose (508 nmol) relative to deprivation (99 nmol) intake, suggesting that mu2 receptors may be mediating maintenance of intake rather than taste effects. Nor-BNI had low ID40 values for intake of sucrose (4 nmol), but not for saccharin (168 nmol), MD (153 nmol) and deprivation (176 nmol), suggesting that kappa receptors may mediate ingestion of sweet-tasting stimuli. That delta (naltrindole: ID40 = 60 nmol), but not delta 1 (DALCE: ID40 = 288 nmol) antagonists consistently reduce saccharin intake suggests a role for the delta 2 receptor subtype in the modulation of hedonic orosensory signals.

Topics: Animals; Drinking Behavior; Enkephalin, Leucine-2-Alanine; Injections, Intraventricular; Male; Naloxone; Naltrexone; Narcotic Antagonists; Polysaccharides; Rats; Rats, Sprague-Dawley; Saccharin