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N Khazan

Publications and source records attributed to N Khazan.

16 recordsLinked to original sources
PubMed1979

Spontaneous vs. naloxone-induced abstinence in dependent rats self-administering L-alpha-acetylmethadol (LAAM) or morphine.

Rats maintained dependence by the self-administration of LAAM or morphine. Following the substitution of saline for LAAM, REM sleep was not disrupted, and the frequency of lever pressing for saline self-injections peaked at about 24 hr. In contrast, following the substitution of saline for morphine, REM sleep was suppressed for 24 hr while the frequency of lever pressing for saline self-injections peaked within 8 hr. When abstinence was induced by hourly iv naloxone injections, REM sleep occurrences were suppressed to a similar degree and for similar durations during naloxone-induced abstinence from both morphine and LAAM. These results suggest that the level of physical dependence maintained during self-administration of LAAM and morphine was similar. The relatively mild abstinence syndrome that was seen during saline substitution in LAAM-dependent rats was most likely related to the long plasma half-lives of the pharmacologically active N-demethylated metabolites of LAAM.

Animals↗
PubMed1979

Electroencephalographic and behavioral tolerance to and cross-tolerance between D-Ala2-methionine-enkephalinamide and morphine in the rat.

Rats were given repeated intraventricular (i.vt.) injections of D-enkephalin (20 microgram/4 hr) or morphine (20 microgram/4 hr) for 72 to 96 hr during electroencephalograman(EEG) recording. Initial epileptiform EEG and associated wet-dog shakes occurred following D-enkephalin but not morphine. The epileptoid EEG progressed to a continous high-voltage EEG synchrony similar to morphine and was associated with behavioral stupor. Rapid eye movement sleep was also suppressed. Repeated administration of D-enkephalin or morphine produced tolerance to their effects. When challenged with i.vt. morphine, D-enkephalin-tolerant rats were cross-tolerant to morphine. Likewise, morphine-tolerant rats were cross-tolerant to D-enkephalin. While the morphine-tolerant rats demonstrated a marked abstinence syndrome when challenged with naloxone (10 mg/kg i.p.), no abstinence signs were observed in the D-enkephalin-tolerant rats. The demonstration of tolerance and cross-tolerance between morphine and D-enkephalin suggests a similar mechanism of action, but the differential development of physical dependence may entail different mechanisms or receptor sensitivities for this effect. These findings of similarities and differences in the acute and chronic effects of D-enkephalin and morphine support the contention that heterogenous opiate receptors may mediate their pharmacologic actions.

Animals↗
PubMed1978

Morphine self-administration and EEG power spectra in the rat.

Power spectral analyses were used to study changes in cortical EEG during morphine self-administration in freely-moving dependent rats prepared with chronic cortical and muscle electrodes and with permanent indwelling IV cannulae. As time progressed from a morphine self-injection toward another injection, a significant spectral shift of the EEG to lower frequencies occurred during successive REM sleep episodes. Each morphine self-injection reinstated the predominance of higher frequencies in the EEG spectra. These EEG changes which preceded lever pressing may reflect changes in morphine plasma levels and in the state of the CNS that precede drug-seeking behavior.

Animals↗
PubMed1978

Cortical EEG power spectra associated with sleep-awake behavior in the rat.

Power spectral analyses were used to study cortical EEG activities during sleep-awake behavior in the rat. EEG spectra, both long-time and sequential short-time, derived from EEG during the states of wakefulness, sleep, and REM sleep were qualitatively and quantitatively different. The degree of inter- and intrasubject variability between these spectra was minimal. This experimental model with the rat should allow quantitative delineation of cortical EEG changes produced by psychotropic drugs.

Animals↗
PubMed1977

Head-shake distributions during self-maintained dependence on morphine, methadone, and l-alpha-acetylmethadol (LAAM) in the rat.

Adult female Sprague-Dawley rats were prepared with chronic cortical and muscle electrodes and i.v. cannulas, made tolerant to and physically dependent on morphine, and trained to level press for i.v. morphine self-injections to maintain dependence. Methadone or l-alpha-acetylmethadol (LAAM) was then substituted for morphine in some of these rats. During self-maintained dependence on either morphine or methadone, head shakes appeared and increased in frequency before lever pressing for self-injections. In contrast, there were fewer head shakes during LAAM dependence, which were evenly distributed over the entire duration of the interinjection interval. These findings suggest a relationship between head-shake distributions, drug-seeking behavior and the pharmacodynamics of these three narcotics.

Animals↗
PubMed1977

1-alpha-acetylmethadol (LAAM), methadone and morphine abstinence in dependent rats: EEG and behavioral correlates.

Adult female Sprague-Dawley rats were prepared with chronic intravenous cannulas and cortical and muscle electrodes for recording electroencephalograms and electromyograms, respectively. They were made physically dependent on morphine by automatic intravenous injections and then trained to lever press in order to self-administer morphine on a FR-20 schedule of reinforcement. Upon stabilization of morphine self-administration, one group continued to self-administer morphine, while two other groups were switched to methadone or 1-alpha-acetylmethadol (LAAM) self-administration for an additional five to ten days. Continuous EEG and EMG recordings were collected. Initially, automatic injections of morphine suppressed rapid eye movement (REM) sleep time, then tolerance developed to this effect. REM sleep time in rats self-administering LAAM, methadone or morphine was within the lower limit of the normal range. Following withdrawal, REM sleep was severely suppressed during the first 24 h with morphine and methadone, but only moderately suppressed with LAAM. Increases in lever pressing during withdrawal from morphine and methadone occurred earlier and were more intense and prolonged than for LAAM. The incidence of head shakes peaked earlier and was higher for morphine and methadone during withdrawal than for LAAM. Irritability scores increased for morphine and methadone during the first day of withdrawal, but did not show any increase until the third day for LAAM. These findings suggest that in dependent rats withdrawal from LAAM is less severe than withdrawal from morphine or methadone.

Animals↗
PubMed1975

Electroencephalographic studies on the development of tolerance and cross tolerance to mescaline in the rat.

Recordings of the electroencephalogram (EEG) and the electromyogram (EMG) were collected continuously from rats equipped with permanent cortical and temporalis muscle electrodes. Automatic injections of mescaline were administered through indwelling i.p. cannulas at an initial dose of 30 mg/kg every 6 hrs for the first 2 days. This dose was then increased to 60 mg/kg 6 hr which was given for the duration of the study. The initial injections of the mescaline induced an immediate desynchronization of the EEG and behavioral arousal of the rat, which endured for 2-3 hrs. After this time, slow wave (SW) sleep and rapid eye movement (REM) sleep episodes reappeared, with the return of regular alternations of the sleep-wakefulness cycle. Upon continued administration of the drug, partial tolerance to the arousal effects of mescaline developed, which was reflected by a gradual reduction in the latencies to onset of SW sleep and REM sleep. Rats rendered tolerant to mescaline in this manner were found to be cross tolerant to lysergic acid diethylamide (LSD) and N,N-diethyl-tryptamine (DET). In contrast, cross tolerance did not occur to amphetamine, which exerts similar arousal and EEG desynchronizing effects. These results agree with physiological and behavioral studies of tolerance and cross tolerance among hallucinogens and support the usefulness of the EEG as a quantitative indicator of central nervous system function.

Amphetamine↗
PubMed1975

REM sleep distributions in post-addict rats relapsing to morphine self-administration: effects of naloxone subcutaneous pellets.

Female Sprague-Dawley rats were prepared with chronic cortical and temporalis muscle electrodes and i.v. cannulas. They were administered i.v. injections of morphine to produce tolerance and physical dependence, then trained to lever press for i.v. self-injections of morphine (10 mg/kg) to maintain dependence. They were subsequently withdrawn for two weeks, implanted subcutaneously with one or two pellets of naloxone base, 100 mg each, or placebo pellets, returned to the experimental cages and allowed to relapse to self-administration of either saline or morphine. Rats with placebo pellets relapsed to morphine self-administration and reestablished the dependence state. However, rats implanted with naloxone and then permitted to self-administer morphine extinguished their lever pressing ("drug-seeking behavior"). Similar results were obtained with rats implanted with placebo pellets and self-administering saline. The self-injections of morphine by rats implanted with placebo pellets severely suppressed REM sleep and altered its normal distribution. Rats implanted with naloxone pellets and that subsequently extinguished their lever pressing, however, did not exhibit a change in REM sleep distributions. Similarly, self-injections of isotonic saline did not exert an effect on REM sleep distributions. These findings suggest that a correlation between REM sleep distributions, drug-seeking behavior, and morphine-naloxone interaction prevailed.

Animals↗
PubMed1975

Changes in the electroencephalogram and REM sleep time during morphine abstinence in pellet-implanted rats.

Rats were prepared with permanent electrodes for recording the electroencephalogram (EEG) and the electromyogram (EMG) and made morphine dependent by the subcutaneous implantation of morphine pellets. Abstinence was then precipitated by removal of the pellets 72 hours later. The evaluation of continuous EEG and EMG recordings revealed a maximal reduction in the amount of REM sleep and a decline in its EEG voltage output during the first day after pellet removal. Both the duration of REM sleep and its mean integrated EEG voltage returned to the baseline levels by the second day of abstinence. A significant but short-lived REM rebound subsequently followed and was accompanied by a trend toward elevation of the mean EEG voltage. These changes are reminiscent of similar findings in rats withdrawn from morphine administered intravenously (Khazan and Colasanti, 1971, 1972). The smaller magnitude of changes in rats treated with morphine pellets, however, may suggest a lower degree of drug dependence.

Animals↗