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Biomedical subjects

H E Jones

Publications and source records attributed to H E Jones.

At least 19 recordsLinked to original sources
PubMed2001

Buprenorphine treatment of pregnant opioid--dependent women: maternal and neonatal outcomes.

This open-label prospective study examined maternal and neonatal safety and efficacy outcome measures during and following prenatal buprenorphine exposure. Three opioid-dependent pregnant women received 8 or 12 mg sublingual buprenorphine tablets daily for 15-16 weeks prior to delivery. Results showed that buprenorphine in combination with comprehensive prenatal care was safe and effective in these women. Prenatal exposure to buprenorphine resulted in normal birth outcomes, a mean of 4.33 days (minimum possible=4) hospitalization, and a 'relatively mild' neonatal abstinence syndrome comprised primarily of tremors (disturbed), hyperactive moro and shortened sleep after feeding. The infants required no pharmacological treatment. Onset of neonatal abstinence signs occurred within the first 12 h after birth, peaked by 72 h and returned to below pre-12 h levels by 120 h. It is concluded that buprenorphine has potential utility for the treatment of pregnant opioid-dependent women.

Adult↗
PubMed2001

Reinforcing effects of oral cocaine: contextual determinants.

RATIONALE: Although the behavioral, subjective, and physiological effects of oral cocaine have been investigated, its reinforcing effects have not been demonstrated. OBJECTIVE: The primary aims of this study were to examine the reinforcing effects of oral cocaine and determine whether such effects can be influenced by manipulating behavioral requirements following drug ingestion. METHODS: Nine adult volunteers with histories of cocaine abuse were trained to discriminate between orally administered cocaine (100 mg/70 kg) and placebo capsules under double-blind conditions. Following acquisition of cocaine vs placebo discrimination (80% correct), the reinforcing effects of cocaine were determined using two different choice conditions (dependent and independent). Volunteers were first exposed to cocaine and placebo once each with a relaxation activity (sitting in a cushioned chair) and a vigilance activity (performing a computer task). Following exposure to each drug with each activity, volunteers began the dependent choice condition. Every 2 days volunteers chose which drug (cocaine or placebo) they ingested with the vigilance and relaxation activities. Volunteers could not choose the same drug with both activities. This procedure occurred 5 times over a 10-day period. The independent choice condition took place over 2 days. On one day, volunteers chose which drug (cocaine or placebo) they ingested with the relaxation activity and, on the other day (in counterbalanced order), which drug they ingested with the vigilance activity. Volunteers were allowed to select the same drug with both activities. RESULTS: All volunteers successfully acquired the cocaine vs placebo discrimination. In the dependent choice condition, all volunteers significantly chose cocaine over placebo with the vigilance activity and chose placebo over cocaine with the relaxation activity. In the independent choice condition, volunteers significantly chose cocaine over placebo with the vigilance activity (i.e., cocaine functioned as a positive reinforcer in the vigilance context). Interestingly, the independent choice condition also showed that volunteers chose placebo over cocaine with the relaxation activity (i.e., cocaine functioned as a negative reinforcer because it was avoided relative to placebo). CONCLUSION: The study shows that the behavioral requirements following drug ingestion can be a determinant of whether or not oral cocaine functions as a reinforcer in volunteers with histories of cocaine abuse.

Administration, Oral↗
PubMed2001

The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women.

This study examined the effectiveness of short-term contingency management for eliminating cocaine use and increasing full day treatment attendance with pregnant methadone-maintained women randomly assigned to either an escalating voucher incentive schedule (n=44) or non-incentive (n=36) conditions. Full day treatment attendance and urine toxicology for cocaine and heroin were assessed and consequated for 14 days. The escalating voucher incentive schedule significantly increased full day treatment attendance and drug abstinence compared to the non-incentive schedule. These results suggest that reinforcing the co-occurrence of two required behaviors (treatment attendance and abstinence from illicit drug use) is effective, and may be an important adjunct to methadone pharmacotherapy for treating pregnant drug dependent women.

Adult↗
PubMed2000

Nalmefene: blockade of intravenous morphine challenge effects in opioid abusing humans.

No studies have assessed the dose-effect or duration of opioid blockade in opioid abusers produced by oral nalmefene, a micro-opioid antagonist. The present study examined the profile and time course of oral nalmefene blockade of subjective and physiological effects produced by intravenous morphine. To assess these effects, seven opioid abusers received oral nalmefene (0, 50 and 100 mg) followed by intravenous morphine (0, 10 and 20 mg) challenges every 24 h for 96 h using a Latin square randomized cross-over design. The duration of blockade varied by measure and dose. Both 50 and 100 mg nalmefene blocked morphine's effects up to 48 h.

Adult↗
PubMed2000

Caffeine withdrawal increases cerebral blood flow velocity and alters quantitative electroencephalography (EEG) activity.

RATIONALE: Cessation of daily caffeine consumption produces a withdrawal syndrome comprised of subjective symptoms and functional impairment. Few controlled studies have examined the physiological effects of caffeine withdrawal. OBJECTIVE: The present study examined the effect of caffeine withdrawal on cerebral blood flow velocity and quantitative EEG. METHODS: Ten volunteers reporting moderate caffeine intake (mean 333 mg/day) participated in this double-blind study. Subjects completed several tests when maintaining their normal diet (baseline period) and during two 1-day periods during which they consumed caffeine-free diets and received capsules containing placebo (placebo test session) or caffeine (caffeine test session) in amounts equal to their baseline daily caffeine consumption. Blood flow velocity was determined for four arteries: right and left middle (MCA), and right and left anterior (ACA) cerebral arteries using pulsed transcranial Doppler sonography. EEG was recorded for 3 min from eight scalp sites while subjects sat, with eyes closed, in a sound-attenuated electronically shielded chamber. Subjective effects were assessed with questionnaires. RESULTS: Results showed an effect of the placebo (21-h withdrawal) condition compared to the caffeine condition. Placebo significantly increased the mean velocity, systolic velocity and diastolic velocity (cm/s) in all four cerebral arteries. In the MCA, the pulsatility index was significantly decreased following placebo. Placebo significantly increased EEG theta power. Placebo also produces subjective effect changes, including increases in heavy feelings in arms and legs and decreases in ability to concentrate. The caffeine and baseline conditions produced similar results on both the physiological and subjective measures. CONCLUSION: Cessation of daily caffeine consumption produced changes in cerebral blood flow velocity and quantitative EEG. These changes may be related to classic caffeine withdrawal symptoms of headache, drowsiness and decreased alertness.

Adult↗
PubMed2000

Spatial summation in lateral geniculate nucleus and visual cortex.

We have compared the spatial summation characteristics of cells in the primary visual cortex with those of cells in the dorsal lateral geniculate nucleus (LGN) that provide the input to the cortex. We explored the influence of varying the diameter of a patch of grating centred over the receptive field and quantitatively determined the optimal summation diameter and the degree of surround suppression for cells at both levels of the visual system using the same stimulus parameters. The mean optimal summation size for LGN cells (0.90 degrees) was much smaller than that of cortical cells (3.58 degrees). Virtually all LGN cells exhibited strong surround suppression with a mean value of 74%+/-1.61% SEM for the population as a whole. This potent surround suppression in the cells providing the input to the cortex suggests that cortical cells must integrate their much larger summation fields from the low firing rates associated with the suppression plateau of the LGN cell responses. Our data suggest that the strongest input to cortical cells will arise from geniculate cells representing areas of visual space located at the borders of a visual stimulus. We suggest that analysis of response properties by patterns centred over the receptive fields of cells may give a misleading impression of the process of the representation. Analysis of pattern terminations or salient borders over the receptive field may provide much more insight into the processing algorithms involved in stimulus representation.

Animals↗
PubMed2000

Oscillations and long-lasting correlations in a model of the lateral geniculate nucleus and visual cortex.

We have previously developed a model of the corticogeniculate system to explore cortically induced synchronization of lateral geniculate nucleus (LGN) neurons. Our model was based on the experiments of Sillito et al. Recently Brody discovered that the LGN events found by Sillito et al. correlate over a much longer period of time than expected from the stimulus-driven responses and proposed a cortically induced slow covariation in LGN cell membrane potentials to account for this phenomenon. We have examined the data from our model, and we found, to our surprise, that the model shows the same long-term correlation. The model's behavior was the result of a previously unsuspected oscillatory effect, not a slow covariation. The oscillations were in the same frequency range as the well-known spindle oscillations of the thalamocortical system. In the model, the strength of feedback inhibition from the cortex and the presence of low-threshold calcium channels in LGN cells were important. We also found that by making the oscillations more pronounced, we could get a better fit to the experimental data.

Computer Simulation↗
PubMed1999

Phencyclidine- and diazepam-like discriminative stimulus effects of inhalants in mice.

It has been shown that abused solvents, such as 1,1,1-trichloroethane (TCE) and toluene, share certain pharmacological properties with central nervous system depressants, such as alcohol and anesthetic vapors. Several vapors were tested for diazepam (DZ)- and phencyclidine (PCP)-like discriminative stimulus effects to further explore their pharmacological specificity. In DZ-trained mice, methoxyflurane fully substituted, and TCE produced partial substitution. Fluorothyl and toluene produced no appreciable DZ-lever responding at any concentration tested. On the other hand, toluene produced concentration-related partial substitution for PCP, whereas methoxyflurane, TCE, and fluorothyl did not substitute. The substitution of some these vapors for DZ or PCP suggests that, like ethanol, the discriminative stimulus effects of abused solvents partially overlap those of N-methyl-D-aspartate antagonists as well as those of gamma amino butyric acid agonists.

Animals↗
PubMed1999

Slow changes in cytosolic free Ca2+ in Escherichia coli highlight two putative influx mechanisms in response to changes in extracellular calcium.

Free intracellular Ca2+ ([Ca2+]i) in Escherichia coli was measured using the bioluminescent protein aequorin. Overall, the bacteria maintained a tight control on their free [Ca2+]i. The results indicated a slow Ca2+ influx, the magnitude of the initial rise in free [Ca2+]i being dependent upon the concentrations of external Ca2+. This was followed by the slow removal of free Ca2+ until normal levels were restored. Specifically, addition of external Ca2+ (0.25-10 mM) resulted in a gradual rise in intracellular free Ca2+ from a basal level of approximately 272 nM, maximally reaching a peak of 0.85-5.4 microM within 30-40 min. This was followed by a slow fall over the next 30 min, culminating in an oscillatory pattern of free [Ca2+]i (range 0.3-0.7 microM for 0.25 mM external Ca2+). In the presence of EGTA, free [Ca2+]i was dramatically reduced. Neither the influx of Ca2+ nor restoration of intracellular free Ca2+ required protein synthesis. Moreover, preincubation with Ca2+ increased the rising phase of intracellular Ca2+ in response to further exposure to external Ca2+. This was further evidence against a specific adaptation process such as the synthesis of calcium exporters. A putative Ca2+ influx channel was demonstrated in stationary phase cells in particular, which could be blocked by La3+. This channel was consistent with the voltage-activated poly-3-hydroxybutyrate/polyphosphate Ca2+ channels previously detailed by Reusch et al. [23] Even in the presence of La3+, however, the free [Ca2+]i of log phase and stationary phase bacteria still increased two-fold over resting values in response to external Ca2+. This suggested the presence of at least two Ca2+ influx processes, one inhibited by La3+ and the other not.

Aequorin↗
PubMed1999

Assessment of opioid partial agonist activity with a three-choice hydromorphone dose-discrimination procedure.

The discriminative stimulus and subjective effects of opioid mixed agonist-antagonists were assessed in volunteer nondependent heroin users trained in a three-choice drug discrimination procedure to discriminate among the effects of i.m. administration of 2 ml of saline, 1 mg of hydromorphone, and 4 mg of hydromorphone (a morphine-like mu agonist). Other subjective, behavioral, and physiological measures were concurrently collected. The discrimination was readily learned by six of the eight subjects. After training, generalization curves were determined for the following i.m. drug conditions: hydromorphone (0.375-4.0 mg), pentazocine (7.5-60 mg), butorphanol (0.75-6 mg), nalbuphine (3-24 mg), and buprenorphine (0.075-0.6 mg). All five of the test drugs were discriminated significantly or showed trends toward being discriminated as hydromorphone 1 mg-like at one or more dose levels. Hydromorphone showed an inverted U-shaped dose-effect function on the hydromorphone 1 mg-like discrimination. Subjective effect measures produced clearer differentiation among the test drugs than did drug discrimination performance. The present results differ from those of a previous study that observed a close relationship between the results of the discrimination measure and subjective effect measures. The previous study used similar methods and test drugs but different training drugs (e.g., 3 mg of hydromorphone versus 6 mg of butorphanol versus saline). It appears that both the sensitivity of drug discrimination performance to between-drug differences and the relationship between discriminative and subjective effects depends upon the specific discrimination that is trained (e.g., two-choice or three-choice). The present high dose-low dose-saline discrimination procedure appears useful for assessing partial agonist activity. The present data are consistent with partial agonist activity for pentazocine, butorphanol, nalbuphine, and buprenorphine.

Adult↗
PubMed1999

Subjective and physiological effects of intravenous nicotine and cocaine in cigarette smoking cocaine abusers.

The subjective and physiological effects of intravenously administered cocaine and nicotine were compared in 10 cigarette-smoking cocaine abusers. Subjects abstained from smoking at least 8 h before each session. Under double blind conditions, subjects received placebo, cocaine (10, 20, and 40 mg/70 mg), or nicotine (0.75, 1.5, 3.0 mg/70 kg) in mixed order. Physiological and subjective data were collected before and repeatedly after each intravenous drug administration. Subjects also completed a drug versus money multiple-choice procedure in which they chose between that day's drug and 44 monetary values. Both drugs increased blood pressure and heart rate and decreased skin temperature. Nicotine showed a more rapid onset of subjective effects than cocaine. Overall, although both cocaine and nicotine increased subjective ratings of "drug effect", "rush", "good effects", "liking", "high", and "stimulated", only nicotine increased ratings of "bad effects" and "jittery". Although the highest nicotine dose produced greater effects than the highest cocaine dose on most subjective measures, the highest cocaine dose produced somewhat greater ratings of drug liking. At doses that produced comparable ratings of drug effect (40 mg/70 kg cocaine versus 1.5 mg/70 kg nicotine), cocaine produced significantly greater good effects, whereas nicotine produced greater bad effects. All three cocaine doses and the intermediate and high nicotine doses were frequently categorized as producing effects similar to those of cocaine or amphetamine. The drug versus money measure showed that the highest cocaine dose was worth twice as much as the highest nicotine dose. Thus, intravenous cocaine and nicotine can be differentiated by their subjective and reinforcing effects.

Adult↗
PubMed1998

Induction with levomethadyl acetate: safety and efficacy.

BACKGROUND: Levomethadyl acetate hydrochloride (known as LAAM) is a mu-opioid agonist approved for the treatment of opioid dependence. Clinical trials comparing LAAM and methadone have reported lower patient retention rates during LAAM induction; however, this may reflect dose and schedule differences. Few studies have systematically examined LAAM dose induction. This study compared induction with 3 different LAAM dosage levels. METHODS: In a randomized, double-blind trial, male and female opioid-dependent patients (N = 180) were assigned to 1 of 3 LAAM doses. The low-dose (25 mg) induction was constant from the onset of treatment, the medium-dose (50 mg) induction lasted 7 days, and the high-dose (100 mg) induction lasted 17 days. Safety and efficacy were assessed on retention, urinalysis and self-reported drug use, symptoms, and patient ratings of medication adequacy. RESULTS: The high-dose group had significantly fewer illicit opioid-positive urine samples in weeks 3 and 4 as compared with the low-dose group. The high-dose group had significantly lower self-reported heroin craving in weeks 2 and 3. All groups demonstrated significant decreases in illicit drug use, withdrawal symptoms, and depression. There were no between-group differences in retention; however, there was a trend (P = .08) for lower retention and a greater number of agonist adverse effects were observed in the high-dose group. Overall, LAAM doses were well tolerated by most patients. CONCLUSION: Induction with low and medium LAAM doses can be safely and effectively achieved within 7 days. Induction with higher LAAM doses can be safely achieved within 17 days, but may result in greater rates of patient dropout and opioid agonist adverse effects. Therefore, higher doses should be approached more slowly.

Adult↗
PubMed1998

Muscimol-like discriminative stimulus effects of GABA agonists in rats.

The discriminative stimulus effects of GABAergic drugs were evaluated in rats trained to discriminate the direct GABA(A) agonist, muscimol (1.0 mg/kg I.P.), from saline under a two-lever fixed ratio (FR) 32 schedule of food reinforcement. Another direct GABA(A) agonist, THIP, produced full substitution for muscimol, however, at doses producing response rate decreasing effects. Diazepam, an allosteric modulator of GABA-mediated postsynaptic inhibition, yielded a maximum of 50% muscimol-lever responding at a dose that also decreased rates of responding. Partial substitution for muscimol (maximal levels of 71% muscimol-lever responding) was also produced by the GABA agonist progabide. Propofol, an anesthetic that potentiates GABA(A) receptor function, and the GABA uptake inhibitor, tiagabine, produced no greater than 53 and 48% muscimol-lever responding, respectively. Valproic acid, a reversible GABA transaminase inhibitor, failed to substitute for muscimol, and vigabatrin, an irreversible GABA transaminase inhibitor, yielded a maximal 46% muscimol-lever responding. These results demonstrate the pharmacological specificity of muscimol discrimination by showing that only direct agonists for the GABA site on the GABA(A) receptor complex produce full substitution. GABA agonists acting by other mechanisms can be distinguished from muscimol and THIP in this procedure.

4-Aminobutyrate Transaminase↗
PubMed1998

Failure of ibogaine to produce phencyclidine-like discriminative stimulus effects in rats and monkeys.

The discriminative stimulus properties of ibogaine were investigated in rats trained to discriminate phencyclidine (PCP; 2.0 mg/kg, I.P.) from saline under a two-lever fixed-ratio (FR) 32 schedule of food reinforcement. Ibogaine (5.6-17.6 mg/kg, I.P.) showed a complete lack of substitution. Ibogaine (0.5-4.0 mg/kg, I.M.) also failed to generalize in rhesus monkeys trained to discriminate PCP (0.1 mg/kg, I.M.) from sham injection. Lysergic acid diethylamide (LSD), tested as a reference compound, produced partial substitution for PCP in rats and occasioned little responding on the PCP-associated lever in monkeys. These results demonstrate important differences between the behavioral effects of PCP and other types of hallucinogenic drugs such as LSD and ibogaine and do not support the hypothesis that the affinity of ibogaine for the PCP site on N-methyl-D-aspartate (NMDA) receptors plays a major role in its acute behavioral effects.

Animals↗
PubMed1998

Inhalant abuse in pregnancy.

Information from a variety of sources suggests the possibility of adverse effects of maternal inhalant abuse, although a well-controlled, prospective study in this area has not been conducted. One source of this concern is the data from occupational exposure to some of the abused solvents, specifically toluene and TCE, with numerous reports suggesting increased spontaneous abortion and fetal malformations. There are also data suggesting decreased fertility and an increased risk for spontaneous abortion in health care workers exposed to nitrous oxide. The relevance of these studies to problems of inhalant abuse is not clear. Although the chemicals involved are the same, there are many differences in the exposure parameters, the populations exposed, and the types of associated risk factors. Nonetheless, there are more than 100 cases reported in the literature of children born to solvent-abusing mothers. Many of these children were small at birth, and some have craniofacial abnormalities not unlike that seen in children with FAS. In the few studies reporting the findings of follow-up in these children, some evidence has been obtained for retardation in growth and development and for residual deficits in cognitive, speech, and motor skills. Clearly, more research is needed to rule out the concomitant risk factors and to identify specific chemicals and patterns of use associated with adverse effects. Animal studies provide more direct evidence that prenatal exposure to toluene or TCE can produce reduced birth weights, occasional skeletal abnormalities, and delayed neurobehavioral development, even under conditions designed to mimic inhalant abuse patterns. Additional research is needed to identify other chemicals with adverse effects, critical periods of exposure, effects of combinations of inhalants, or interactions with drugs of abuse. The research literature seems sufficient to alert clinicians to possible problems in patients who abuse inhalants while pregnant. Diagnosis and good prenatal care for these women are important. The evidence for neonatal withdrawal is limited at this time; however, infants born to women who have recently used inhalants should be observed carefully for an alcohol-like withdrawal syndrome. Although it is not possible to link a specific birth defect or developmental problem in the child of an inhalant abuser to prenatal exposure to a specific chemical, it is clear that inhalant abuse and its associated lifestyle place children at increased risk. A wider appreciation of this is needed among health care professionals and the general public.

Anesthetics, Inhalation↗
PubMed1998

Evaluation of the reinforcing and discriminative stimulus properties of the low-affinity N-methyl-D-aspartate channel blocker memantine.

Memantine (MEM) is currently in clinical use in Europe for the treatment of various neurological disorders. It is a low-affinity channel blocker of N-methyl-D-aspartate (NMDA) receptors whose voltage-dependent, rapid binding kinetics are believed to limit its phencyclidine (PCP)-like side effects. MEM, and its analog amantadine (AMA), which has also been demonstrated to have some NMDA antagonist activity, were evaluated for PCP-like behavioral effects. The discriminative stimulus properties of MEM and AMA were tested in monkeys and rats trained to discriminate PCP from saline using a standard two-lever drug discrimination paradigm under a fixed ratio (FR) schedule of food reinforcement. In rats, MEM resulted in a dose-dependent substitution for PCP; however, full substitution occurred only at response rate suppressing doses. AMA failed to substitute for PCP at any dose tested. For MEM, all four monkeys showed complete substitution for PCP at doses which did not greatly decrease rates of responding. Conversely, AMA occasioned little or no responding on the PCP-associated level in any of the subjects. Intravenous self-administration of MEM and AMA was tested under a FR schedule of reinforcement in four monkeys trained to lever press for infusions of PCP. MEM served as a reinforcer in all subjects at one or more doses tested. For two of the subjects, at least one dose of AMA maintained rates of self-administration above those for saline. For both MEM and AMA, maximal response rates were considerably lower than with PCP self-administration and both drugs were much less potent in monkeys than would be predicted from rodent studies. The data show that MEM shares discriminative stimulus effects with PCP under these testing conditions, whereas the chemically similar compound AMA does not. MEM also serves as a positive reinforcer in rhesus monkeys, whereas AMA can serve as a weak reinforcer in only some subjects. Both AMA and MEM are reported to function as NMDA antagonists, yet clear differences exist in their behavioral effects with MEM acting more like a PCP-like antagonist. In addition, despite the rapid channel kinetics of MEM's NMDA receptor blockade, it may have some PCP-like abuse potential in humans at doses above the normal therapeutic levels.

Amantadine↗