I Nir

Hebrew University of Jerusalem, Yerushalayim, Jerusalem District, Israel

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Publications (45)201 Total impact

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    ABSTRACT: The effect of high ambient temperature (34 degrees C) on the function of the female reproductive system, on embryonic development and on outcome of pregnancy, was investigated in heat-exposed sham-operated (Sh) and pinealectomized (Px) golden hamsters maintained under short photoperiod. Plasma prolactin levels were reduced in both heat-exposed groups (ShH and PxH) but pituitary prolactin was increased in the pinealectomized groups irrespective of ambient temperature (21 or 34 degrees C). Pituitary weights and LH contents were not affected in any test group. Heat exposure brought about a reduction in the number of corpora lutea and of pups born, the latter being more drastically reduced in absence of the pineal; the depressant effect of heat on ovarian weight was evident only in the pinealectomized animals. Progesterone levels were not affected in any test group and pregnancy was not prolonged, thus, it would seem that pregnant hamsters adapt themselves well to heat. Moreover, high ambient temperature promoted a rise in pineal. HIOMT activity and boosted cortisol levels in presence of the pineal gland only, which, together with the above findings, shows that the pineal can provide protection for pregnant hamsters against adverse effects of high ambient temperature.
    Journal of Neural Transmission 02/1988; 73(1):57-63. DOI:10.1007/BF01244622 · 2.87 Impact Factor
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    ABSTRACT: Acute treatment with delta 1-tetrahydrocannabinol (delta 1-THC) elevated the concentration of beta-endorphin-like immunoreactivity (beta-ELIR) in plasma and in the hypothalamus, but not in the hippocampus of rats habituated to the injection procedure. These effects were not obtained with the psychotropically inert analog of delta 1-THC, cannabidiol. In animals that had not been habituated to the injection procedure, placebo treatment induced a decrease in hippocampal beta-ELIR.
    Experientia 05/1987; 43(4):413-5. DOI:10.1007/BF01940432
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    ABSTRACT: delta 1Tetrahydrocannabinol (THC) acutely suppresses tonic serum luteinizing hormone (LH) and prolactin levels in adult male rats. The exact site of its action has not been identified. We have performed complete hypothalamic deafferentation (CHD), which disrupts the medial basal hypothalamus (MBH) from the rest of the CNS, but did not abolish the ability of THC to suppress hypothalamic-pituitary responses in gonadectomized male rats. This was shown by the equal reduction in serum levels of LH and prolactin in non-deafferented (ND) and CHD animals. These results indicate that THC is able to act inside the MBH and that the MBH-pituitary axis remains responsive to its inhibitory effect despite interruption of the neural connections between the MBH and extrahypothalamic areas. However, the corticotropin releasing factor neurons in the MBH appear functionally impaired as a result of the transection and become unresponsive to the normally produced THC stimulation. Different patterns of action seem to govern the various hypophyseal hormones controlled by the hypothalamus, suggesting that the release of LH releasing hormone and prolactin inhibiting factor might be maintained by the activity of neurons surviving inside the island.
    Experimental Brain Research 02/1985; 59(2):213-6. DOI:10.1007/BF00230899 · 2.17 Impact Factor
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    ABSTRACT: A low and a high dose of 1-Tetrahydrocannabinol ( 1-THC) and of cannabidiol (CBD) were IP injected in rats that had been isolated for 7 days. Forty-five minutes after injection, the rats were tested for social interactions with non-isolated, untreated test partners in dyadic encounters under standardized conditions. Different aspects of social behavior were analyzed. The high dose of 1-THC (10 mg/kg) prevented nearly all social interactions. The low dose of 1-THC (1 mg/kg) exerted selective and specific effects on social interactions. Social contact behavior, including crawl over/mounting, and social grooming, and aggressive behavior, including fighting, kicking, and biting, were markedly decreased, whereas social exploratory behavior (exploration of the partner and anogeniaal investigation) and the behavioral item, approach/follow, were hardly affected by 1-THC treatment. Both doses of CBD (2 and 20 mg/kg) failed to change the various aspects of social interaction. It is postulated that the effects of 1-THC on close and intimate contact behavior of rats may contribute to the understanding of marihuana taking in humans.
    Psychopharmacology 01/1984; 84(4):561-565. DOI:10.1007/BF00431467 · 3.99 Impact Factor
  • Isaac Nir, Nisan Hirschmann
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    ABSTRACT: A potentiated production of [14C]melatonin ([14C]Mt) with a simultaneous decline in [14C]serotonin ([14C]5-HT) conversion to its final metabolite [14C]5-hydroxyindole acetic acid ([14C]5-HIAA) was recorded in a rat pineal medium cultured with [14C]tryptophan and either a neuroleptic [haloperidol (HAL) or chloropromazine (CPZ)] or an antidepressant [desipramine (DIP)] drug. A difference between the pharmacological groups of drugs was evident only in [14C]5-HT levels, which were found significantly elevated in the presence of the neuroleptic HAL and reduced in the presence of the tricyclic antidepressant DIP. A parallel trend was observed in norepinephrine (NE)-induced [14C]tryptophan metabolism in the pineal culture medium. All three drugs tested brought about further enhancement of NE-induced synthesis of MT; HAL produced an elevated, but DIP a reduced, level of [14C]5-HT, compared to the NE-induced value.
    Biochemical Pharmacology 08/1983; 32(14):2139-41. DOI:10.1016/0006-2952(83)90218-6 · 4.65 Impact Factor
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    ABSTRACT: Exposure of pinealectomized rats to high ambient temperature (35 degrees C; PXH) brought about a diminution in pituitary weight and LH content when compared to their sham-operated peers (35 degrees C) or to pinealectomized controls (22 degrees C). Serum corticosterone level of PXH rats was significantly depressed while heat or pinealectomy alone had no effect. Mean oestrous cycle length was prolonged and blood serum progesterone was increased in the heat-exposed rats. However, the extended oestrous cycles and elevated serum progesterone levels of heat-exposed rats were depressed or abolished by pineal ablation. Thus, the pineal appears to exert a moderating effect on heat-induced endocrine changes in female rats. No changes were noticed in uterine and ovarian weights corrected for body weights either on the day of vaginal opening, at occurrence of the oestrous phase expressed as percentage of total oestrous cycle, or in N-acetyltransferase and hydroxyindole-O-methyltransferase activities.
    Hormone Research 02/1983; 17(4):222-7. DOI:10.1159/000179701 · 2.48 Impact Factor
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    ABSTRACT: 1.1. Chronic exposure of golden hamsters (Mesocricetus auratus) to a high ambient temperature (34°C) depresses body weight as well as the weights of the interscapular brown adipose tissue and several endocrine glands.2.2. In some instances pinealectomy prevented-completely or partially—the effect of heat on the endocrine glands, indicating a role for the pineal in moderating some heat-induced endocrine changes.
    Comparative Biochemistry and Physiology Part A Physiology 02/1983; 74(3):649-51. DOI:10.1016/0300-9629(83)90561-3 · 2.17 Impact Factor
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    ABSTRACT: Decreased testicular weight with damaged seminiferous tubules were observed in hamsters pinealectomized and exposed continuously to high ambient temperature. In hamsters with intact pineals, exposure to heat resulted in reduced testicular weight without recognizable histological damage. In both groups, serum testosterone levels were elevated, evidently through a compensatory mechanism in the interstitial cells, which did not appear to be damaged. Concomitantly with these findings, reduced serum LH, and pituitary LH and prolactin concentrations were encountered in the heat-exposed pinealectomized hamsters, compared to those of their heat-exposed sham-operated counterparts. These results in hamsters reaffirm a previous postulation of a moderating, protective role for the pineal, against adverse effects of prolonged exposure to heat, in rodents.
    Journal of Neural Transmission 02/1983; 58(3-4):261-70. DOI:10.1007/BF01252811 · 2.87 Impact Factor
  • I Nir, M Puder
    Harefuah 04/1982; 102(6):258-61.
  • I Nir, N Hirschmann
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    ABSTRACT: Serum and pituitary LH, prolactin and progesterone changes recorded in parturient rats exposed to continuous darkness throughout pregnancy were not prevented by early ablation of the pineal gland. Similarly, the shorter gestation period observed in rats kept in continuous darkness and the overwhelming tendency of rats in general to deliver during the light period (real or subjective), persisted in the pinealectomized animals. Darkness-induced endocrine changes in rat dams during the perinatal period appear not to be mediated by the pineal gland.
    Hormone Research 02/1982; 16(6):385-91. DOI:10.1159/000179529 · 2.48 Impact Factor
  • I Nir, N Hirschmann
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    ABSTRACT: Exposure of rats to continuous darkness throughout gestation produced a threefold increase in their serum prolactin and a moderate one in their serum LH levels on the day preceding delivery. Parallel decreases in pituitary prolactin and LH contents were experienced indicating enhanced release of the hormones. In the animals kept in constant light only prolactin release was increased before delivery, their LH levels were unaffected, although diminished pituitary contents due to decreased synthesis were evident. Following parturition the photo-induced prolactin levels in serum and pituitary disappeared, but the LH values of the rats exposed to both extremes of illumination persisted, in contrast to those of the control animals kept in alternating light (12 L : 12 D) whose values fell abruptly. Serum oestradiol was affected neither by darkness nor light but serum progesterone concentrations were depressed before delivery in the rats kept in darkness even more than in the control animals. Exposure to continuous darkness shortened the duration of gestation. The marked tendency to deliver during the daytime hours was not influenced by exposure to continuous darkness but was completely abolished by constant light. It is suggested that the strongly decreased serum progesterone levels--possibly brought about by the high prolactin concentrations observed before parturition--may be contributing to the earlier onset of delivery in the rats exposed to continuous darkness.
    Journal of Neural Transmission 02/1982; 55(2):157-68. DOI:10.1007/BF01243758 · 2.87 Impact Factor
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    ABSTRACT: Adult male rats, either intact (N) or bearing complete hypothalamic deafferentations (CHD), were injected with delta 1-tetrahydrocannabinol (THC: 5 mg/kg BW, IP). Forty-five minutes later, they were decapitated and trunk blood was collected for serum ACTH and corticosterone (CS) determinations. In the N animals, serum levels of both ACTH and CS were markedly elevated in the drug-treated, as compared to the vehicle-treated group (approximately 8-fold and 10-fold, respectively). In CHD rats, on the contrary, THC administration did not significantly alter serum concentrations of either ACTH or CS. These results demonstrate (1) that acute treatment with THC stimulates the secretion of ACTH as well as of CS; and (2) that extrahypothalamic sites and/or neural pathways mediate this effect.
    Experimental Brain Research 02/1982; 46(1):85-8. DOI:10.1007/BF00238101 · 2.17 Impact Factor
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    ABSTRACT: The effects of the pineal gland on endocrine function (especially those of the gonads) were investigated in male rats chronically exposed to increased temperature. Weanling male rats were either pinealectomized (Px) or sham-operated (Sh). Following one week of recovery, animals were assigned to either control temperature of 21 +/- 1 degree C (PxC and ShC) or a temperature of 35 +/- 1 degrees C (PxH and ShH). The animals were kept at their respective temperature for at least 30 days. In both groups (PxH and ShH) exposure to increased temperature resulted in a significant reduction in body and hypophysial weights, and in serum LH and testosterone levels as compared with the respective controls (PxC and ShC). Rectal temperature and serum corticosterone were also significantly increased. No changes were found in pineal hydroxyindole-O-methyltransferase activity of sham-operated rats kept in increased temperature (ShH vs. ShC). Pinealectomy alone (PxC vs. ShC) did not alter any of the measured parameters, except for increased pituitary LH content. Increased temperature plus pinealectomy (PxH vs. PxC; and PxH vs. ShH) caused a significant reduction in pituitary LH content and further accentuated (PxH vs. ShH) the diminished serum LH and testosterone levels evoked by exposure to high temperature. The results suggest that in male rats the pineal gland may play a role in moderating the changes in the reproductive processes that are induced by increased temperature.
    Journal of Neural Transmission 02/1981; 50(2-4):267-73. DOI:10.1007/BF01249147 · 2.87 Impact Factor
  • I Nir, N Hirschmann
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    ABSTRACT: Pinealectomy leads to significantly higher levels of progesterone (on days 19 and 20 of gestation) and oestradiol (on days 21 and 22) in the serum of pregnant rats. These results indicate that during the last phase of pregnancy the pineal gland may be modifying the levels of gonadal hormones, although not affecting the sequence of the physiological events.
    Experientia 03/1980; 36(2):259-60. DOI:10.1007/BF01953769
  • I Nir, N Hirschmann
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    ABSTRACT: Following melatonin implants into pregnant rats throughout the entire period of gestation, the prenatal level of LH was significantly lowered in serum and the pituitary, while that of prolactin was enhanced in serum and diminished in the pituitary. After parturition, most of the melatonin-induced changes in LH and prolactin disappeared, being replaced by compensatory stimulation of release and synthesis of LH and inhibition of release of prolactin. Neither the abrupt physiological decline of serum progesterone, nor the enhanced level of oestrogen present during the period preceding delivery seem to be affected by melatonin. The findings were observed in both sham-operated (control) and pinealectomized animals, thus suggesting that melatonin exerts its inhibitory action on hypothalamic LH-RH and PIF not by utilizing an additional antigonadotropic pineal factor and not by the steroid sex hormones.
    Journal of Neural Transmission 02/1980; 49(4):219-28. DOI:10.1007/BF01252127 · 2.87 Impact Factor
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    ABSTRACT: (1) Δ1-Tetrahydrocannabinol (Δ1-THC), the major psychoactive ingredient of cannabis, prevents ovulation when administered at 14:00 hr to pro-oestrous rats . Δ6-Tetrahydrocannabinol (Δ6-THC), a psychoactive isomer of Δ1-THC, was a less potent inhibitor of ovulation . However, the potent psychoactive 5′-(1″,2″ dimethylheptyl) (DMH) homologue of Δ6-THC (Δ6-THC-DMH) had a 60-fold higher ovulation-blocking potency than the parent compound and about 15 times higher potency than Δ1-THC. Moreover, the action of Δ6-THC-DMH was more prolonged than that of Δ1-THC, being expressed even when the compound was administered at 08:00 hr on the day of pro-oestrus, i.e. 6 hr before the critical period for neural triggering of ovulation. (2) (+) Cannabidiol [(+)CBD] was only weakly active as an ovulation blocker and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl equatorial) (compound 2a) and 5,6-dihydro-7-hydroxy-2-isopropyl-5-methyl-9-pentyl-2,6-methano-2H-1-benzoxocin-4(3H)-one (C5 methyl axial) (compound 3a) were inactive, but substitution of a DMH side chain for the amyl side chain of these three compounds resulted in significant enhancement of ovulation-inhibiting activity. (−)CBD and its DMH homologue did not affect ovulation in pro-oestrous rats. (3) (+) CBD-DMH (which showed ovulation inhibiting activity in the rat) has been found to be devoid of psychotropic activity when tested in rhesus monkeys (10 mg/kg). Apparently a separation between psychotropic and hormonal activity in the cannabinoids is possible.
    Psychoneuroendocrinology 01/1980; 5(1):53–62. DOI:10.1016/0306-4530(80)90009-8 · 5.59 Impact Factor
  • I Nir, N Hirschmann
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    ABSTRACT: A thin-layer chromatographic procedure for measuring pineal HIOMT activity is described, based on the methylation of NAS to melatonin. The method enables simple and accurate determination in small aliquots from a single pineal organ homogenate.
    Experientia 12/1979; 35(11):1426-7. DOI:10.1007/BF01962763
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    ABSTRACT: Hexosemonophosphate shunt and phosphorylase activities determined in the pineal glands of rats during mid-light and mid-darkness periods were found to undergo diurnal rhythms. A high active hexosemonophosphate shunt -- indicated by the more ready conversion of CO2 of the glucose carbon in position 1 than of that in position 6 -- was found to correlate to the function of endocrine activity of night time/darkness. Phosphorylase activity, indicating glycogenolysis, measured at the same times, was found to be increased during the period of mid-light when basal metabolism is high compared to that during mid-darkness. The significance of these findings is discussed.
    Life Sciences 09/1979; 25(6):515-20. DOI:10.1016/0024-3205(79)90563-0 · 2.30 Impact Factor
  • I Nir, N Hirschmann
    Progress in brain research 02/1979; 52:421-35. DOI:10.1016/S0079-6123(08)62948-9 · 5.10 Impact Factor
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    ABSTRACT: Serum LH levels were higher in pinealectomized than in sham-operated control rats during all 4 of the last days of pregnancy studied, although reaching significance only during the final 2 days, 21 and 22. Prolactin (Prl) levels in the serum on the final day of pregnancy, and its contents in the pituitary throughout the entire study period, were significantly lower in pinealectomized rats. Pituitary weights were lower in pinealectomized than in control animals during days 21 and 22 of pregnancy, but no differences were found between the 2 groups in the average number of living foetuses and resorptions. The results presented would seem to indicate that during the last phase of pregnancy the pineal gland plays a role in the modification of gonadotropin synthesis and release. It appears that with LH the release, and with Prl mainly the synthesis, is being affected by the pineal, although the release of Prl may be influenced as well.
    Neuroendocrinology 02/1979; 28(1):44-51. · 4.93 Impact Factor

Publication Stats

469 Citations
201.00 Total Impact Points


  • 1969–1985
    • Hebrew University of Jerusalem
      • • School of Pharmacy
      • • Department of Pharmacology
      Yerushalayim, Jerusalem District, Israel
  • 1984
    • Utrecht University
      Utrecht, Utrecht, Netherlands