Concurrent heroin self-administration and intracranial self-stimulation in rats

In a two-lever testing chamber, rats lever pressed for lateral hypothalamic brain stimulation or intravenous heroin reinforcers on a concurrent FR1 FR1 schedule of reinforcement. Responding for stimulation did not alter the rate of heroin self-administration, and responding for heroin caused increased responding for stimulation. Discontinuing heroin injections, or administering 3 mg/kg of naloxone, disrupted responding for both reinforcers, while changing the unit dose of heroin did not appreciably affect response rates for stimulation. This experiment demonstrates that rats are able to lever press during the period between successive self-administered heroin infusions, suggesting that the pausing normally seen between infusions is not due to debilitation, stereotyping, or sedation.     

Hypnotic analgesia in conditions of stress is partially reversed by naloxone

In this study the hypothesis that hypnotic analgesia under conditions of stress is mediated through a neurochemical mechanism involving the release of opioid peptides in the CNS was investigated.Ten highly hypnotizable subjects participated in a 2×2 factorial design, which involved hypnotic analgesia, stress and double blind administration of naloxone (an opiate antagonist) or placebo. Analysis of post-hypnosis results indicates that hypnotic analgesia was significantly reversed by the interactive effects of stress and naloxone. It is inferred that stress may be the common psychological denominator of the various analgesic methods which effectively engage this endogenous pain inhibitory system. Additional analyses of anxiety measures reveals no significant association between trait and state anxiety, but significant relationships between state anxiety and time tolerance to ischemic pain. These results suggest that anxiety remains a definitional problem and that previous conceptualizations may not have satisfactorily explained the affect's adaptive function.     

The dependence of the anti-nociceptive effect of morphine and other analgesic agents on spinal motor activity after central monoamine depletion

The interference of central monoamine depletion with the anti-nociceptive effect of morphine, pethidine and aminophenazone was studied in rats with regard to the changes in spinal motor activity induced by reserpine, tetrabenazine and α-methyl-p-tyrosine.All three analgesic agents prolonged the time of the tail-flick reaction in intact rats. This effect was abolished by reserpine, which prolonged the reaction time. Bilateral lesioning of the substantiae nigrae with microinjections of 6-hydroxydopamine prolonged the reaction time and abolished the anti-nociceptive effect of morphine. In spinal rats, the time of the tail-flick reaction was prolonged by morphine and reduced by aminophenazone. Reserpine did not abolish the effect of morphine in spinal rats.Morphine, pethidine and aminophenazone inhibited the α-reflex discharges facilitated by conditioning stimulation in intact and spinal rats. Pethidine and aminophenazone, but not morphine, depressed the facilitation of α-reflex discharges produced by central monoamine depletion in intact rats. The increase in the amplitude of monosynaptic mass reflexes produced by reserpine in intact rats was not reduced by morphine, whereas the depression of polysynaptic mass reflexes after reserpine was antagonized by morphine.The three analgesic agents differ markedly in their action on spinal motor activity altered by monoamine depletion. It is concluded that the antagonizing effect of central monoamine depletion on the anti-nociceptive effect of morphine, pethidine and aminophenazone in the rat is due to a change in the basal motor activity on which the spinal nociceptive reflex is elicited.     

Hypothalamic opioids and the acute-phase glycoprotein response in guinea pigs

Endogenous opioids (EO) probably do not modulate endotoxin (LPS)- or interleukin 1 (IL1)-induced fever because naloxone does not prevent its development. Yet, increases in CSF and hypothalamic levels of beta-endorphin have been reported during LPS-and IL1-induced fevers. Since IL1 also reduces the specific binding of opioids to their receptors in guinea pig brain, the opioids could be involved in modulating nonfebrile effects of IL1. To determine whether EO might have a role in the IL1-induced acute-phase glycoprotein response of guinea pigs, (1) naloxone (5 and 10 mg/kg, SC) was injected prior to LPS (S. enteritidis 2 micrograms/kg, IV; N = 5), and (2) morphine (MOR, 10 micrograms/microliter), [D-ala2]-met-enkephalinamide (DAME, 5 micrograms/microliter), or dynorphin A (DYN, 5 micrograms/microliter) was injected into the preoptic area (1 microliter, bilaterally; N = 8/treatment) or into the 3rd ventricle (N = 4/treatment); pyrogen-free saline was the control injection. Measurements were: core temperature (Tco) and, as indices of acute-phase glycoproteins, plasma levels of copper (Cu) and N-acetylneuraminic acid (NANA). Naloxone did not prevent the fever or the increases in plasma Cu and NANA levels evoked by LPS. The intracerebral administration of opioid agonists by either route induced variable rises in Tco, each with a different pattern, but no increases in plasma Cu and NANA levels. Thus, EO do not participate in the central modulation of acute-phase glycoprotein synthesis, but may have a role in influencing other nonthermal IL1 effects in the CNS.     

Possible non-narcotic component to action of opiate peptides on tonic immobility

Chickens were tested in a tonic immobility paradigm after a single intraperitoneal injection of either 0.0, 0.1, 1.0, 10.0; 100.0, or 1000.0 microgram/kg of the potent opiate analog, (D-Ala2, F5Phe4)-Met-enkephalin-NH2. An inverted-U relationship was obtained, with 100 microgram/kg being the most effective in prolonging immobility. This dose was used in subsequent studies involving pretreatment with naloxone or diluent followed by treatment with diluent, (D-Ala2, F5Phe4)-Met-enkephalin-NH2 (a strong opiate), or (D-Phe4)-Met-enkephalin (a weak opiate). The results indicated that although naloxone had mixed effects in attenuating the duration of tonic immobility, even the analog with negligible opiate activity reliably potentiated the response. Therefore, a component of the effect of opiate peptides on tonic immobility could be due to a non-narcotic action.     

Gas chromatography-mass spectrometry in forensic chemistry for identification of substances isolated from tissue

Summary The use of combined gas chromatography-mass spectrometry in forensic chemistry is demonstrated in 13 cases where various substances had to be isolated and identified, the substance was present in small amounts in some samples while in others the sample available was very small. In other instances a rapid and certain identification was important. The results are compared with data obtained by conventional procedures. The advantage of this method is discussed and it is emphasized that a collection of mass spectra of all common substances searched in forensic chemistry simplifies the indentification. Reference mass spectra of some drugs are given.

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Zusammenfassung Die Anwendung einer kombinierten gaschromatographischen und massenspektrophotometrischen Methode in der gerichtlichen Chemie wurde anhand von 13 untersuchten Fällen diskutiert. Verschiedene Substanzen, z.T. in kleinsten Mengen, wurden isoliert und identifiziert. Die erhaltenen Ergebnisse werden mit den Resultaten der konventionellen Methoden verglichen, zudem wird anf die Vorteile der GC-MS-Kopplung hingewiesen. Gleichzeitig werden einige Massenspektren wiedergegeben.Eine Massenspektrensammlung von den in der gerichtlichen Chemie häufig anzutreffenden Substanzen ist für eine rasche und einfache Identifizierung erforderlich.

     

Weight loss and shock-elicited aggression as indices of morphine abstinence in rats

Weight loss and shock-elicited aggression have been compared as quantitative indices of morphine abstinence in rats. A range of doses of morphine was administered to rats by i.p. injection twice daily for 12–15 days. After injections were stopped, morphine-abstinent rats lost weight precipitously, and showed an increased frequency of fighting in response to aversive stimulation (foot-shock). Recovery of weight appeared complete after 15–20 days but a significant increase in aggression was found at 18 days post-withdrawal; this virtually disappeared after 52 days. Both the amount of weight lost and the frequency of fighting increased as a function of the previous maintenance dose of morphine; the effective dose range appeared similar for these two indices. Weight loss was much less variable than fighting, had the advantage of rapid, objective measurement, and appeared to be the more reliable index of abstinence.     

Influence of naloxone and methysergide on the analgesic effect of clomipramine in rats

The effects of the tricyclic antidepressant clomipramine were studied in two analgesic tests in rats: (1) vocalization threshold response; and (2) scored behavioral response to electric shock to the tail. Clomipramine (20-50 mg/kg i.p.) produced analgesia, decreasing behavioral response scores and increasing vocalization threshold. Morphine also reduced the response scores in the second test. Naloxone (0.8 mg/kg i.p) or methysergide (20 mg/kg i.p.) (no effect when given alone) abolished the analgesic effect of clomipramine as evaluated by vocalization threshold response. Naloxone alone (0.6 or 2 mg/kg i.p.) increased the behavioral response at 20 and 30 V but did not modify the score at 40 V. Naloxone reduced the analgesic effect of clomipramine or morphine in the behavioral test. These results suggest that the analgesic effect of clomipramine could involve both serotonergic and endorphin central systems.     

Naloxone does not antagonize leukocytic pyrogen

In a crossover experiment, cats were given third cerebral ventricular injections of 500 microgram naloxone hydrochloride or saline vehicle followed in 15 min by i.v. injections of saline solution or leukocytic pyrogen. The pyrogen produced comparable fevers after both saline and naloxone pretreatment. Intravenous administration of naloxone hydrochloride (5 mg/kg) likewise did not prevent febrile responses to leukocytic pyrogen. These results indicate that endogenous opioid peptides are not likely central mediators of pyrogen-induced fevers.     

Fatal combined anileridine-pethidine poisoning. A gas chromatography,thin layer chromatography and mass spectrometry investigation

Summary Anileridine and pethidine were established by gas and thin layer chromatography and mass spectroscopy. In the mass spectrum the main peak of anileridine is found at m/e 246 and that of pethidine at m/e 71. The determination was made by gas chromatography from the blood, urine, liver, muscle and stomach contents.

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Zusammenfassung Anileridin und Pethidin wurden mittels Gas- und Dünnschicht-chromatographie sowie massenspektroskopisch festgestellt. Im Massenspektrum liegen die Hauptspitze von Anileridin bei m/e 246 und diejenige von Pethidin bei m/e 71. Die Bestimmung erfolgte gaschromatographisch aus Blut, Harn, Leber, Muskel und Mageninhalt.