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Biomedical subjects

B H Herman

Publications and source records attributed to B H Herman.

At least 19 recordsLinked to original sources
PubMed1995

The effects of NMDA receptor antagonists and nitric oxide synthase inhibitors on opioid tolerance and withdrawal. Medication development issues for opiate addiction.

This article is an exploration of the National Institute on Drug Abuse (NIDA) Technical Review on the role of glutamatergic systems in the development of opiate addiction. The effects of "glutamate antagonist" medications on opioid tolerance and withdrawal are examined. In rodents, mu opioid tolerance can be inhibited by noncompetitive N-methyl D-aspartate (NMDA) receptor antagonists [MK801, dextromethorphan (DM), ketamine, phencyclidine (PCP)], competitive NMDA receptor antagonists (LY274614, NPC17742, LY235959), partial glycine agonists (ACPC), glycine antagonists (ACEA-1328), and nitric oxide synthase (NOS) inhibitors [L-NNA, L-NMMA, methylene blue (MB)]. Similarly, some of the symptoms of opioid withdrawal observed in opioid-dependent rodents also can be inhibited by noncompetitive NMDA receptor antagonists (MK801, DM, ketamine), competitive NMDA receptor antagonists (LY274614), glycine antagonists (felbamate), and NOS inhibitors (L-NNA, L-NMMA, L-NAME, L-NIO, 7-NI, MB). There are some serious toxicological effects associated with the administration of some of the noncompetitive NMDA receptor antagonists in rodent but not in squirrel monkey brain, and some medications induce PCP-like behavioral effects. The medications with the most immediate clinical appeal are those that could be coadministered with methadone to decrease mu opioid tolerance and dependence; they include DM, MB, 7-NI, ACPC, and ACEA-1328.

Animals↗
PubMed1994

Effects of the opiate antagonist, naltrexone, on binging antecedents and plasma beta-endorphin concentrations.

The effects of the opiate receptor antagonist, naltrexone, were examined on antecedent thoughts of binging and plasma beta-endorphin concentrations in an adolescent girl who was hospitalized with bulimia nervosa. Significant decreases in urge to binge were obtained during naltrexone administration compared with control sessions. Baseline plasma beta-endorphin concentrations for the bulimic adolescent were not different from those of nonbulimic controls, but plasma beta-endorphins increased significantly during naltrexone administration. After discharge from the hospital, the adolescent refused to take naltrexone because she felt she could not deal with her life without the "pleasure of binging." The case points to the interplay of biological and psychological factors in bulimia nervosa.

Adolescent↗
PubMed1993

A brain-tumor model utilizing stereotactic implantation of a permanent cannula.

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.

Animals↗
PubMed1990

A novel biochemical model linking dysfunctions in brain melatonin, proopiomelanocortin peptides, and serotonin in autism.

A novel biochemical model for autism is presented, which proposes that a subgroup of autistic individuals may have a hypersecretion of pineal melatonin that produces a cascade of biochemical effects including a corresponding hyposecretion of pituitary proopiomelanocortin (POMC) peptides and a hypersecretion of hypothalamic opioid peptides and serotonin (5-HT). The model is reviewed, and supporting animal and clinical research, is summarized. The first arm of the model suggests that increases in pineal melatonin results in hypersecretion of 5-HT in hypothalamus and blood. The second arm of the model indicates that hypersecretion of melatonin also inhibits the release of hypothalamic corticotrophin-releasing hormone (CRH). Hyposecretion of CRH may result in decreased release of both pituitary B-endorphin (B-E) and adrenocorticotrophin hormone (ACTH); this, in turn, may result in decreased plasma concentrations of B-E, ACTH, and cortisol. In autism, a genetically determined hypersecretion of hypothalamic B-E may further contribute to an inhibition of pituitary B-E because of negative feedback inhibition. Therefore, autism may reflect a dysfunction in the pineal-hypothalamic-pituitary-adrenal axis which, modulates POMC and 5-HT systems of the brain. This model is consistent with numerous clinical investigations implicating hypersecretion of brain 5-HT and opioid peptides in autism. The model may have heuristic importance in guiding future research in the biochemistry of autism.

Autistic Disorder↗
PubMed1990

Effects of the opiate antagonists diprenorphine and naloxone and of selected opiate agonists on feeding behavior in guinea pigs.

Opiate-sensitive feeding behavior has now been demonstrated in a number of species. We sought information on which opioid receptors might be involved in the observed feeding behaviors. Guinea pigs are known to have higher concentrations of the opioid kappa receptor than any other laboratory animal, so we compared the feeding suppressive potency of the general opiate antagonist, diprenorphine to that of the relatively more mu-specific antagonist, naloxone in that species. We found that diprenorphine was over twenty times more effective than naloxone in suppressing feeding in guinea pigs, suggesting the importance of receptors other than mu in feeding initiation in the guinea pig. Confirmatory evidence for the role of kappa receptors was sought, but not found, in comparisons of the effectiveness of different types of opiate agonists in promoting feeding in these animals. These agonists suppressed, rather than stimulated feeding. We conclude that no feeding stimulatory effects of opiates can be demonstrated in guinea pigs. This observation may indicate that opioids play little role in the natural regulation of feeding in this species or that opioids result in prolonged sedation during which the animals fail to eat. The greater feeding suppressive potency of diprenorphine, a general opiate antagonist, versus naloxone, a mu-preferential antagonist, indicates that to whatever extent opiates are involved in guinea pig feeding, the opiate effect is probably not a mu receptor effect.

Animals↗
PubMed1990

A possible role of proopiomelanocortin peptides in self-injurious behavior.

1. The hypothesis that opioids may be involved in self-injurious behavior is supported by fifteen years of basic animal research suggesting that opioid peptides of the brain and spinal cord participate in the modulation of antinociception in animals, and research of animal models for self-injurious behavior utilizing exogenously administered opiate agonists. 2. Clinical biochemical and pharmacological research conducted over the past five years has also suggested the possibility that opioid peptides may play an important etiological role in the elaboration of self-injurious behavior in some individuals. 3. An opioid overactivity self-injurious hypothesis is supported by results of one study indicating elevated Fraction II opioids (enkephalins) in the lumbar-thecal cerebrospinal fluid of self-injurious children compared to controls, and by the five out of six published studies demonstrating statistically significant decreases in the frequency of self-injurious behavior with the opiate antagonist, naltrexone. 4. A very recent investigation has suggested that some self-injurious individuals show abnormalities in their plasma proopiomelanocortin peptide response to naltrexone, thereby indicating a possible dysfunction in the responsitivity of the proopiomelanocortin system of the hypothalamic-pituitary-adrenal axis of these individuals. 5. These data and results of other investigations have resulted in the elaboration of the original opioid hypothesis to a more comprehensive biochemical model that focuses on this proopiomelanocortin dysregulation. 6. Because of biochemical and functional interrelationships between proopiomelanocortin peptides and certain other neurochemical systems in the brain, it is proposed that pineal melatonin and serotonin may also be involved in this dysregulation. Further basic and clinical research will be needed to test the proposed biochemical model for self-injurious behavior.

Aggression↗
PubMed1990

Cerebrospinal fluid and plasma beta-endorphin-like immunoreactivity in full-term neonates and in preterm neonates with and without apnea of prematurity.

Beta-endorphin-like immunoreactivity (B-ELI) was measured in cerebrospinal fluid (CSF) and plasma from infants of postnatal age 24 h to 70 days. Three groups were examined: 17 were of postconceptual age greater than or equal to 37 weeks, 16 were postconceptual age less than or equal to 35 weeks without apnea and 10 were of postconceptual age less than or equal to 35 weeks with apnea. All infants were clinically stable. Two-way analysis of variance between groups showed no difference in the concentration of B-ELI in CSF or plasma, or in the CSF/plasma B-ELI ratio. Concentrations of B-ELI in plasma were significantly higher in infants of postnatal age 1-3 weeks and greater than or equal to 4 weeks, than in infants of postnatal age less than 1 week. We conclude that, in nonstressed infants, there is no relationship between the concentration of B-ELI in CSF or plasma and a concurrent diagnosis of apnea of prematurity. Our data indicate that a significant developmental increase occurs in the plasma concentration of B-ELI after the first week of life.

Aging↗
PubMed1989

Role for opioid peptides in self-injurious behavior: dissociation from autonomic nervous system functioning.

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opioid receptor antagonist, on self-injurious behavior (SIB), heart rate, and blood pressure in three males (one 10-year-old and two 17-year-olds) were investigated. Subjects were evaluated in a structured test session for SIB. The frequency of the most predominant type of SIB (head and face hitting) was significantly reduced by naltrexone (maximum was 71% at the 1.5 mg/kg dose), while self-biting was not significantly decreased at any dose. In contrast, naltrexone had no significant effect on heart rate or blood pressure. Based upon these and other results it was concluded that naltrexone produced decreases in specific SIBs by blocking opioid receptors in brain, and that such opioid blockade had no effect on two measures of cardiovascular function.

Adolescent↗
PubMed1989

Effects of acute administration of naltrexone on cardiovascular function, body temperature, body weight and serum concentrations of liver enzymes in autistic children.

The effects of acute, orally administered naltrexone (0.5, 1.0, 1.5 and 2.0 mg/kg), a potent opiate receptor antagonist, on auscultated heart rate, systolic blood pressure and axillary body temperature were investigated before and about 1 h postdrug in 5 autistic children (4-12 years of age). In addition, an electrocardiogram was recorded on each child before and about 3 h after placebo or 2.0 mg/kg of naltrexone. Finally, the serum concentrations of the liver enzymes glutamic-oxaloacetic transaminase (SGOT) and glutamic-pyruvic transaminase (SGPT) were measured 24 h following placebo or naltrexone administration. Naltrexone had no statistically significant effects on any of these measures in comparison with baseline or placebo levels. Thus, these data provide preliminary evidence for the safety of acute administration of naltrexone in children.

Alanine Transaminase↗
PubMed1988

Ontogeny of beta-endorphin and cortisol in the plasma of children and adolescents.

The ontogeny of plasma beta-endorphin (B-E) and cortisol concentrations was studied in normal children (3-11 yr old) and adolescents (12-18 yr old) of several ethnic backgrounds. The morning plasma concentrations did not significantly differ as a function of sex or age for either B-E [males (n = 88), 7.19 +/- 0.39 (+/- SE) pmol/L; females (n = 73), 6.80 +/- 0.50 pmol/L] or cortisol [males (n = 87), 383 +/- 14 nmol/L; females (n = 69), 359 +/- 20 nmol/L]. There was a small but significant positive correlation between plasma B-E and cortisol concentrations. When sampled immediately after venipuncture, there were no significant differences in the plasma B-E or cortisol concentrations of children who cried during venipuncture compared with those who did not. These data suggest that morning plasma B-E and cortisol concentrations are constant throughout childhood, adolescence, and into early adulthood.

Adolescent↗
PubMed1987

Naltrexone decreases self-injurious behavior.

The effect of naltrexone (0.5, 1.0, 1.5, and 2.0 mg/kg) on the frequency of self-injurious behavior (SIB) was investigated in three male adolescents. The frequency of total SIB was reduced significantly in all three subjects; dose-dependent decreases (at 0.5, 1.0, and 1.5 mg/kg) in SIB frequency were observed in the two mentally retarded subjects. These data suggest a role for opioid peptides in SIB.

Adolescent↗
PubMed1985

Antinociception and paralysis induced by intrathecal dynorphin A.

Intrathecal administration of dynorphin A in rats produced dose-dependent antinociceptive effects in the tail-flick test to radiant heat and on a limb-flexion test to pressure. The potency of dynorphin A as an analgesic agent on the tail-flick test was dependent upon the duration of cannula implantation. When a short-term procedure was used (drug injected 1 day after catheter implantation) dynorphin A was approximately equipotent to morphine, whereas in animals with long-term implants (drug injected 7 or more days after catheter implantation) dynorphin A was an order of magnitude less potent than morphine. [D-Ala2,D-Leu5]enkephalin was the most potent opioid tested, and in the tail-flick test (long-term procedure) it was about 2 orders of magnitude more potent than dynorphin A and 7 times more potent than morphine. [Leu]enkephalin had no detectable antinociceptive effects. Low doses of naloxone (1 and 2 mg/kg s.c.) completely blocked the antinociceptive effects of morphine and [D-Ala2,D-Leu5]enkephalin, but neither low nor high (40 mg/kg s.c.) doses clearly blocked the antinociceptive effects of dynorphin A. Thus, dynorphin A has an antinociceptive action at the level of the spinal cord, and mu opioid receptors do not mediate these effects. In addition, high doses of dynorphin A (20 nmol or greater) produced long-lasting hindlimb paralysis, which suggests that dynorphin peptides may play a role in motor function in the spinal cord. This paralytic action of dynorphin A was not antagonized by naloxone in doses up to 32 mg/kg s.c.

Animals↗
PubMed1984

Repeated administration of naltrexone and diprenorphine decreases food intake and body weight in squirrel monkeys.

Although chronic administration of naloxone has been reported to reduce food intake and body weight in rats, there have been no comparable investigations using a nonhuman primate. We examined the effects of repeated injections of two long acting opiate antagonists - naltrexone and diprenorphine - on the ad libitum intake of a nutritional complete liquid diet and on body weight in squirrel monkeys. Naltrexone binds with highest affinity to the mu opioid receptor whereas diprenorphine binds with equally high affinity to several subtypes of opioid receptor. Diprenorphine (ED50 = 0.01 mg/kg) was 22 times more potent than naltrexone (ED50 = 0.22 mg/kg) in decreasing 2 h food intake, suggesting that more than one opioid receptor subtype may be involved in the anorectic effects of opiate antagonists. A 1.0 mg/kg dose of drug reduced 24 h food intake by 50% and was associated with a weekly reduction in body weight of 4 and 5% for naltrexone and diprenorphine, respectively. Thus, in contrast with shorter time intervals, 24 h food intakes were similar for the two drugs, and this was associated with comparable body weight profiles. The decreases in food intake and body weight remained constant over the period of drug administration. Some monkeys showed profuse salivation and "wet dog shakes" after 4 days of treatment with the 1.0 mg/kg dose but not after 1 day. Therefore, opiate antagonists given chronically to monkeys reduced food intake and body weight in a dose-dependent manner with no evidence of tolerance to these effects.

Animals↗
PubMed1983

Comparison of electrical resistance, bubble withdrawal, and stereotaxic method for cannulation of cerebral ventricles.

A comparison was made of three methods of lateral intraventricular (LV) cannulation in the rat brain. Rats in a control group (n = 8) were cannulated using traditional stereotaxic coordinates. In a second group (n = 8), electrical resistance was used to localize the ventricle and differentiate it from surrounding brain areas. In a third group (n = 8), a bubble withdrawal technique was employed where movement of a bubble in polyethylene tubing was monitored as the cannula was lowered in brain. All three methods produced accurate LV cannulation, but the electrical resistance technique was associated with optimal placement within the LV. Using the resistance procedure, greater access was obtained to posterior portions of the ventricular system. Also described is a novel stereotaxic cannula holder that may be used in the bubble withdrawal procedure or in obtaining acute samples of cerebrospinal fluid.

Animals↗
PubMed1981

Ascending endorphin inhibition of distress vocalization.

Distress vocalizations were produced in adult guinea pigs by electrical stimulation of the dorsomedial thalamus or the septum-preoptic area. Both of these forebrain-derived vocalizations were increased by systemic administration of naloxone and were inhibited by analgesic periventricular gray stimulation. Naloxone blocked the inhibitory effects of the analgesic stimulation on thalamic vocalizations. Stimulation of nonanalgesic mesencephalic sites in close proximity to the periventricular gray increased the anterior-elicited vocalizations. These data provide evidence for ascending endorphin-mediated inhibition of excitatory forebrain sites for distress vocalizations.

Animals↗
PubMed1981

Opioid modulation of ingestive behavior.

Supportive evidence for an important role of endogenous opioid systems in modulation of ingestive behaviors is presented. Low doses of morphine (1.0-5.0 mg/kg) increase and low doses of naloxone (0.5-2.5 mg/kg) decrease food and water intake during both acute and chronic testing in mildly-deprived rats. Chronic infusions of naloxone with implanted osmotic mini-pumps elicited sustained dose-related suppression of food, water, and saccharin solution intakes but did not reduce ingestion of 10.0% glucose solution or food following 12 hr deprivation. Finally, naloxone treatment did not antagonize nocturnal ingestion of food any more than it reduced day time feeding when the latter was enhanced by prior food deprivation. These results indicate that an opiate agonist and an opiate antagonist modify ingestive behaviors oppositely, affirming that endogenous opioid systems may be involved in control of feeding and drinking. However, their role may be restricted to only indirect participation in homeostatic regulation via neural systems modulating emotional tone or goal-directed behaviors in general.

Animals↗
PubMed1980

Endogenous opioids and social behavior.

Evidence for the hypothesis that brain-opioids mediate social affect and social attachments is summarized. Opiates and opioids are very effective in reducing social separation-induced distress vocalizations (DVs), in puppies, young guinea pigs and chicks, while opiate antagonists can increase DVs. In studies of specific social behaviors in rodents, morphine (at doses 1 mg/kg and below) decreases proximity maintenance time in socially housed animals, increased play, decreases maternal aggression but has no effect on pup retrieval. Naloxone reduces play and disrupts pup-retrieval, but has no consistent effect on proximity maintenance time of socially housed animals. In young rats tested in social learning situations, morphine delays and naloxone hasten extinction. These data are consistent with the proposition that brain opioids modulate social emotions and behaviors.

Aggression↗