Down-regulation of hypothalamic 5-HT1A receptors in morphine-abstinent rats

The effects of morphine tolerance-dependence and abstinence on 5-HT1A receptors in brain regions and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact (tolerant-dependent) and in the other they were removed (abstinent). Rats were killed, and spinal cords and brains were excised. Brain was dissected into seven regions (amygdala, hippocampus, hypothalamus, striatum, midbrain, pons + medulla and cortex). 5-HT1A receptors were characterized by using [3H]8-hydroxy-di-n-propylaminotetralin [( 3H]DPAT) as the ligand and unlabelled 5-HT to determine the non-specific binding. In morphine and placebo tolerant-dependent rats the binding of [3H]DPAT to 5-HT1A receptors in brain regions and spinal cord did not differ. The Bmax value of [3H]DPAT in the hypothalamus of morphine abstinent rats was decreased by 61.9%. No change in Bmax value was observed in other brain regions and spinal cord. The Kd values were unaffected. Subcutaneous administration of DPAT produced hypothermia in rats from which pellets had been removed. The intensity of DPAT-induced hypothermic response was greater in morphine abstinent rats as compared to placebo abstinent rats. Since DPAT is believed to have a major action on the presynaptic 5-HT neurons, it is concluded that in morphine abstinent rats 5-HT1A receptors are down-regulated in hypothalamus, but in morphine tolerant-dependent rats they are unaffected.     

Syringomyelia-like manifestation of subacute combined degeneration.

A 32-year-old male presented with progressive weakness and numbness of both upper limbs of one-month duration. The patient had weakness and wasting of small muscles of both hands with weak grip. Sensory system revealed graded sensory loss to pain, temperature and touch in C5 to T1 distribution and vibration and joint position sense from C5 to C8 in the both upper limbs. There was areflexia in the upper limbs while there was no motor or sensory deficit in the lower limbs. The cortical potential on stimulation of posterior tibial nerve was prolonged on both sides. On MR imaging of the cervical spine there was iso to low intense lesion which was hyperintense on T2-weighted imaging along the dorsal aspect of the cord extending from C2 to C6 level. The axial images showed involvement of the posterior column. The serum vitamin B12 level was found to be low. The patient responded to parenteral cyanocobalamine therapy and the radiological lesion subsequently resolved.     

Evaluation of xanthotoxol for central nervous system activity.

Xanthotoxol (XT), 8-hydroxypsoralen, exhibited dose-graded sedative activity in dogs, cats, rats, mice and hamsters. At doses of 5-20 mg/kg intraperitoneally (i.p.) in cats and 3-100 mg/kg orally (p.o.) in dogs, XT blocked predatory mouse/rat killing behavior. In mice, XT (10-300 mg/kg i.p.) exhibited a dose-dependent reduction in locomotor activity but was less potent in this regard than reference diazepam (10-100 mg/kg i.p.). XT in mice (0.1-10.0 mg/kg i.p.) and in hamsters (0.1-10.0 mg/kg p.o.) antagonized amphetamine-induced hypermobility but was less potent than diazepam. XT elevated the electrical threshold in foot-shock-induced fighting behavior in rats. XT (0.1-30.0 mg/kg p.o.) potentiated pentobarbital-induced narcosis in hamsters at otherwise subeffective doses of pentobarbital. Conditioned avoidance responses in rats were not significantly altered with 1-3 mg/kg i.p. and 30-100 mg/kg p.o. doses of XT but 300 mg/kg p.o. blocked both conditioned and unconditioned response. Doses of 100-1000 mg/kg i.p. of XT in mice were used to study 48-h acute toxicity of XT and its LD50 was estimated to be 468 mg/kg. Doses of 10, 40 and 80 mg/kg p.o. were used to study the chronic toxicity of XT in rats for 6 months and no side effects or abnormalities in reproductive activity or endocrine integrity were noted. The F1 generation of rats from 6-month XT-treated parents were free of teratogenic effects.     

Fat embolism syndrome following bone marrow harvesting

A case of fat embolism syndrome is reported following an uncomplicated bone marrow harvest. The presenting symptoms were restlessness, shortness of breath and arterial hypoxemia. A lung perfusion scan ruled out the presence of a lung thromboembolism. The patient received supportive therapy and recovered within a few hours. We speculate that the larger gauge needle (13 vs 15) used to aspirate the bone marrow may have represented increased trauma to the iliac crest leading to fat embolism.     

Prognosis of acute renal failure in children: a multivariate analysis

Various factors were analyzed in 80 consecutive children under 16 years who had acute renal failure (ARF), for various prognostic factors. Overall mortality was 42.5%, with significantly higher levels seen in hemolytic uremic syndrome (68%, P <0.05) and associated with cardiac surgery (90.9%, P <0.01). Anuria (67.6% vs. 43.5%, P <0.05), need for dialysis (85.3% vs. 56.5%, P <0.05), neurological complications (50% vs. 6.3%, P <0.01), and respiratory complications (35.2% vs. 2.1%, P <0.01) were significantly higher in nonsurvivors than survivors. Multiple regression analysis showed the presence of neurological and respiratory complications to be poor prognostic factors. Received May 2, 1995; received in revised form August 28, 1996; accepted September 13, 1996     

Effect of melanotropin release inhibiting factor on changes by haloperidol and centbutindole in cerebral cortical 5-hydroxytryptamine receptors

The effect of melanotropin release inhibiting factor (Pro-Leu-Gly-NH2, MIF) was determined on changes induced by two neuroleptics, haloperidol and centbutindole, in cerebral cortical 5-hydroxytryptamine (5-HT) receptors. Male Sprague-Dawley rats were injected daily i.p. with vehicle, haloperidol (1.0 mg/kg) or centbutindole (0.5 mg/kg), respectively, for 21 days. On day 22, these 3 groups were further divided into 2 subgroups and injected with either vehicle or MIF (2.0 mg/kg, i.p.) daily for 3 days. 3H-5-HT was used to study 5-HT1 receptors, and 3H-spiroperidol to label 5-HT2 receptors in the cerebral cortex. Chronic administration of haloperidol significantly increased (39.7%) the maximal binding capacity (Bmax) of 3H-5-HT binding to 5-HT1 receptors. Dissociation constant (Kd) values did not change. Centbutindole had no effect on 5-HT1 receptors. MIF had no effect on 5-HT1 receptors, nor did it alter haloperidol-induced increases in the Bmax of 3H-5-HT binding to 5-HT1 receptors. Chronic administration of centbutindole significantly increased (61.1%) the Bmax of 3H-spiroperidol binding to 5-HT2 receptors. No change occurred in the Kd values. Chronic treatment with haloperidol had no effect on 5-HT2 receptor characteristics. MIF had no effect on 5-HT2 receptors or on the increase in 5-HT2 receptor density induced by centbutindole. The behavioral syndrome induced by 5-hydroxytryptophan (5-HTP) (50, 100 and 200 mg/kg, i.p.) was also measured in rats treated chronically with haloperidol or centbutindole. Haloperidol had no effect on the 5-HTP syndrome, whereas centbutindole stimulated by 24-45% the intensity of the syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)