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L S Harris

Publications and source records attributed to L S Harris.

At least 19 recordsLinked to original sources
PubMed1992

The acoustic startle response as a measure of behavioral dependence in rats.

A series of experiments was conducted to assess the sensitivity of the acoustic startle response to chronic morphine administration and naloxone-precipitated withdrawal. Rats were implanted with two subcutaneous pellets containing either 75 mg each of morphine or containing only placebo. In experiment 1, withdrawal induced by 0.05-0.2 mg/kg naloxone dose-dependently decreased the magnitude of the startle response. Physical dependence was confirmed by a naloxone-induced acute weight loss seen in morphine-implanted rats, but naloxone had no effect on startle or body weight in non-dependent animals. In experiment 2, a modified procedure with fewer trials per session and fewer test days was employed. Naloxone (0.2 mg/kg) given 4-5 days after implantation induced large startle-response decreases in morphine-dependent rats while having no effect in placebo-implanted rats. Post-naloxone saline tests revealed no significant differences in startle between morphine and placebo groups. Startle scores were significantly higher in morphine-implanted rats than in placebo rats during a saline test given 3 days following pellet implantation. In a separate group of animals, however, acute IP injections of morphine from 0.3-10 mg/kg had no significant effect on startle amplitude. The effect of repeated pairings of withdrawal with the startle environment was assessed in experiment 3. Morphine-dependent rats startled significantly less if naloxone injections were given before the startle session than if they were administered 4 h later. Conditioned withdrawal effects, expressed during a final test session when all rats received saline, were observed for the body-weight measure but not for the startle response.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustic Stimulation↗
PubMed1992

Sudden death associated with aortitis and fibrosclerosing disease of the conduction system.

Aortitis is known to complicate a number of autoimmune diseases and syphilis. In most patients with autoimmune disease, arthritis is the initial presentation followed by aortic insufficiency. We report two cases of ostensibly healthy, middle-aged men in whom the initial manifestation of aortitis was sudden death. In each patient, there was extension of inflammation from the aorta into the atrioventricular node. These cases emphasize the importance of examining the conducting system in cases of sudden death associated with aortitis and no grossly evident cause of death. To our knowledge, this is the first report of aortitis presenting as sudden death.

Aortitis↗
PubMed1991

Postmortem magnetic resonance images of the injured brain: effective evidence in the courtroom.

Magnetic resonance images (MRI) of the whole, formalin-fixed brain produce details of pathologic changes deep within brain substance not apparent on external examination. Photographs of these radiographic images present pathologic features in a black-and-white, 2-dimensional format which has proven particularly effective in court before judge and jury. This pathologist has noted acceptance of such photographs in explaining to jurors the details of his testimony in selected cases where brain trauma resulted in a wrongful death. Penetrating missile wounds and blunt impact injuries are particularly well documented by this method.

Brain↗
PubMed1991

Common stereospecificity of opioid and dopamine systems for N-butyrophenone prodine-like compounds.

The two optical isomers of 1-[3-(p-fluorobenzoyl) propyl]-3-methyl-4-phenyl-4-propionoxypiperidine (FPP) were obtained by resolution of (+/-)-r-3-methyl-4-phenyl-c-4-piperidinol followed by N-alkylation and O-propionylation. These, as well as the racemate, were evaluated for their antinociceptive, opioid, and neuroleptic properties using in vivo and in vitro test systems. The results are remarkable in two respects, namely, the dextrorotatory isomer is consistently the most potent on all tests, and it acts on both opioid (mu) and neuroleptic (D2) receptors.

Alphaprodine↗
PubMed1990

Intravenous self-administration of 4-methylaminorex in primates.

The reinforcing effects of (+/-)-cis-2-Amino-4-methyl-5-phenyl-2-oxazoline (4-methylaminorex) were determined in two models of intravenous drug self-administration in primates. In baboons, lever pressing was maintained under a fixed-ratio (FR) 80- or 160-schedule of intravenous cocaine delivery (0.32 mg/kg per injection). Each drug injection was followed by a 3-h time-out allowing a maximum of 8 injections per day. Vehicle or 4-methylaminorex doses were substituted for cocaine for a period of 15 or more days. One of the two 4-methylaminorex doses evaluated (0.32 mg/kg per injection) maintained self-administration behavior above vehicle control levels in all four animals. This dose of 4-methylaminorex maintained cyclic patterns of self-injection behavior across days and produced signs of psychomotor stimulant toxicity. In rhesus monkeys, 4-methylaminorex (0.0003-0.1 mg/kg per injection) was made available to animals trained to self-administer cocaine (0.01 or 0.033 mg/kg per injection) under an FR 10 schedule of reinforcement during daily 1-h sessions. Each of the three monkeys self-administered at least two doses of 4-methylaminorex at rates exceeding those maintained by vehicle injections. Taken together with reports of recreational abuse of 4-methylaminorex, the present results indicate that this drug has a potential for abuse similar to that of other psychomotor stimulants.

Animals↗
PubMed1989

Assessment of the abuse potential of acetorphan, an enkephalinase inhibitor.

The discriminative stimulus properties, reinforcing effects and physical dependence potential of acetorphan, a parenterally-active enkephalinase (E.C. 3.4.21.11) inhibitor, were assessed in the present studies. Rats trained to discriminate 2 mg/kg morphine from saline did not generalize to acetorphan at any dose tested (5-50 mg/kg). Acetorphan also had minimal reinforcing effects in rhesus monkeys. When acetorphan was substituted for cocaine, one dose (300 micrograms/kg per inj.) maintained responding somewhat above the range of vehicle values in only two of the four monkeys tested. In physical dependence studies, acetorphan also failed to produce opioid-like effects. In morphine-dependent monkeys and rats, acetorphan failed to suppress withdrawal. Additionally, there were no overt withdrawal signs observed following the termination of chronic acetorphan infusion in the rat. Together, these results indicate that acetorphan appears to have minimal abuse potential.

Animals↗
PubMed1989

Very long-acting narcotic antagonists: the 14 beta-p-substituted cinnamoylaminomorphinones and their partial mu agonist codeinone relatives.

The biological activity of 14 beta-(p-halo and p-methylcinnamoylamino)-7,8-dihydro-N-cyclopropylmethylnorcodei nones and their corresponding morphinones was investigated. In vitro, the codeinones displayed predominantly mu agonist activity in the 3H-etorphine binding assay and mouse vas deferens preparation. In vivo, in the mouse, the compounds showed weak to inactive antinociception in the tail-flick and hot-plate tets; however, they were potent agonists in the phenylquinone test and moderately weak antagonists in the tail-flick vs morphine test. They also substituted for morphine in withdrawn morphine-dependent rhesus monkeys. When given to non-withdrawn morphine-dependent monkeys, the codeinones precipitated a delayed but long-lasting withdrawal syndrome. They all generalized to codeine in the drug-discrimination test in rhesus monkeys and, in the dose range tested, two compounds were self-administered. This activity is consistent with that of a partial mu agonist. On the other hand, all the morphinones had very long-acting and highly potent mu antagonist properties. The data can be reconciled by assuming that the codeinones are partially metabolized to their respective morphinones. These compounds may be especially useful in the treatment of opioid dependence.

Analgesics↗
PubMed1986

Cytologic results of fine-needle aspiration biopsies of the central nervous system.

The cytologic results of 34 fine-needle aspiration (FNA) biopsies of the central nervous system (CNS) are reported. There were 31 intraoperative biopsies performed at the time of craniotomy. All the cases were diagnosed using direct smear preparations stained with Papanicolaou and Diff-Quik (Harleco, NJ) stains. The sensitivity of the procedure was 90.7%, specificity 100%, positive predictive value 100%, and efficiency of the test of 91%. There were no false-positive diagnoses and three false-negative diagnoses. This study attests to the diagnostic accuracy of FNA cytologic examination of the central nervous system. Statistical analysis of the few previous FNA biopsy series of the CNS are presented. Review of the indications, advantages and complications of CNS needle biopsy are discussed. This report supports the role of fine-needle aspiration cytology in the evaluation of CNS lesions. With recent developments in radiologic imaging, especially ultrasound and computed tomography (CT) using stereotactic guidance, specimens can be obtained for cytologic diagnosis using thinner needles. Excellent diagnostic accuracy can be obtained, as pathologists gain greater familiarity with interpreting FNA biopsy material. Other advantages of FNA biopsy of the central nervous system include the low morbidity and mortality of the procedure and the ability to perform the biopsy through a burr hole under local anesthesia and thereby decrease hospitalization time and cost.

Adult↗
PubMed1986

The stimulants and hallucinogens under consideration: a brief overview of their chemistry and pharmacology.

The substances under review are a heterogeneous set of compounds from a pharmacological point of view, though many have a common phenylethylamine structure. Variations in structure lead to marked changes in potency and characteristic action. The introductory material presented here is meant to provide a set of chemical and pharmacological highlights of the 28 substances under consideration. The most commonly used names or INN names, Chemical Abstract (CA) names and numbers, and elemental formulae are provided in the accompanying figures. This provides both some basic information on the substances and a starting point for the more detailed information that follows in the individual papers by contributors to the symposium.

Animals↗
PubMed1986

Self-administration of methylenedioxymethamphetamine (MDMA) by rhesus monkeys.

Four rhesus monkeys trained to press levers for intravenous cocaine infusions were tested with saline and (+/-)-3,4-methylenedioxymethamphetamine (MDMA; 3-300 micrograms/kg per infusion) during daily 1-h sessions. From four to over nine times more cocaine infusions were obtained than saline infusions during baseline sessions. When MDMA was substituted for cocaine, at least one dose was self-administered in 3 of the 4 monkeys at rates that exceeded the range of saline infusions. In fact, two of the monkeys self-administered a dose of MDMA at a greater rate than cocaine. These results demonstrate that MDMA can serve as a positive reinforcer for rhesus monkeys and, taken together with other preclinical behavioral studies, suggest a potential for recreational use of MDMA by humans.

3,4-Methylenedioxyamphetamine↗