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Biomedical subjects

J D Lane

Publications and source records attributed to J D Lane.

At least 37 records · Page 2Linked to original sources
PubMed1995

Dopamine release during cocaine self-administration in rats: effect of SCH23390.

This experiment tested the hypotheses that: (1) self-administration of cocaine would produce an increase in dopamine (DA) oxidation current in the nucleus accumbens (n. acc.); and (2) a faster rate of cocaine intake in the presence of a D1 receptor antagonist would produce a greater increase in DA levels. Rats trained to self-administer cocaine under a fixed-ratio 2 schedule were implanted with stearate-modified graphite paste electrodes bilaterally in the n. acc. The effect of pretreatment with the D1 receptor antagonist, SCH23390, on the DA oxidation current associated with self-administration of cocaine (1 mg/inj.) or saline was investigated using chronoamperometry. Pretreatment with SCH23390 produced a 2-fold increase in the amount of cocaine intake. This in turn resulted in a 2-fold increase in the DA oxidation current recorded in the n. acc. Pretreatment with SCH23390 did not, however, produce any significant change in either the number of saline injections received or the DA oxidation current recorded during saline self-administration. These findings show that cocaine increases DA oxidation currents in the n. acc., and that both the rate of cocaine self-administration and the magnitude of these currents increase even further following SCH23390. The results also imply that the baseline rate of cocaine self-administration does not result in the occupation of all possible DA transporter sites.

Animals↗
PubMed1995

mRNA translocation and microtubules: insect ovary models.

The nurse cells in insect ovarioles supply the developing oocytes with various cellular components, including mRNAs, which pass from one cell to the other through intercellular bridges traversed by microtubules. Best studied of these mRNAs are those that encode the axis-determining factors in Drosophila embryos. These mRNAs are further translocated and localized within the oocyte to sites where the products of their translation will ultimately function. This article explores the evidence supportive of a role for microtubules and motor proteins in these processes.

Journal Article↗
PubMed1994

Small bowel biopsy through an enteroclysis catheter to augment findings at enteroclysis and hypotonic duodenography.

Proximal jejunal mucosal biopsy was performed by a radiologist through the nasojejunal catheter at the time of enteroclysis. Seventeen patients (10 men and seven women, aged 23-73 years [mean, 46 years]) were studied with enteroclysis because of clinical signs of malabsorption with suspected small bowel disease. In seven (41%) patients, results at biopsy were positive, and results in another seven (41%) were positive at enteroclysis. In 10 (59%) patients, results were positive at one or both tests. Performance of both small bowel biopsy and enteroclysis at the same session is feasible and offers additional clinically pertinent information than can be obtained at enteroclysis alone.

Barium Sulfate↗
PubMed1993

Parameters of self-administration of cocaine in rats under a progressive-ratio schedule.

Progressive-ratio (PR) schedules may provide a more direct measure of drug-reinforcing efficacy than the more traditionally used fixed-ratio schedules. Under a PR schedule, an increasing number of lever presses is required for the delivery of each successive reinforcer. However, there have been few studies of fundamental parameters of cocaine self-administration under a PR schedule. This study was undertaken to assess if PR responding using cocaine reinforcement in rats would: a) be acquired rapidly; b) be maintained on a stable baseline for long periods; and c) provide data on the effect of changing the dose of cocaine that are amenable to statistical analysis. In addition, the effects of pretreatments with SCH23390, a D1 receptor antagonist, or ondansetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were tested against several doses of cocaine. Stable performance of PR cocaine self-administration (0.90 mg/kg) was acquired within 10 training sessions and was maintained for over 50 training sessions. Increasing the dose of cocaine from 0.10-2.70 mg/kg resulted in a directly related increase in a) the number of reinforcers obtained, b) the highest ratio completed, and c) the interreinforcer time (ISRT: time between each cocaine infusion). In terms of statistical analysis, the number of reinforcers obtained was found to be preferable to the highest ratio completed as a measure of breakpoint. Pretreatment with SCH23390 significantly reduced the breakpoint; this reduction was not due to a motor-incapacitating effect of SCH23390 because the ISRT showed a tendency to be shortened by SCH23390. Pretreatment with ondansetron failed to significantly affect either the number of reinforcers obtained or the ISRT. These results show that rats can readily acquire the task of self-administration of cocaine under a PR schedule and maintain a stable baseline for an extended period. Further, a PR schedule appears to be suitable for the study of pharmacological treatments that might affect cocaine self-administration. Simultaneous monitoring of the breakpoint and of the ISRT determines if a decrease in the breakpoint is the result of a motor-incapacitating side effect of the pretreatment.

Animals↗
PubMed1993

Tolerance to self-administration of cocaine in rats: time course and dose-response determination using a multi-dose method.

To assess tolerance to cocaine in a self-administration paradigm, rats were trained to self-administer cocaine (0.25 mg/injection) on a fixed-ratio 2 (FR2) schedule of reinforcement. The development of tolerance was studied during chronic administration of cocaine (20 mg/kg per 8 h for 10 days), given either contingently (self-administered by the rats) or non-contingently (infused by the experimenter). Both contingent and non-contingent administration of cocaine produced comparable tolerance, as indicated by a faster rate of cocaine self-administration (the average inter-reinforcer time, ISRT, decreased significantly). Tolerance developed by day 2 of the chronic regimen and reached a floor value (60% of baseline) from day 4 through day 10. Termination of chronic cocaine then resulted in recovery from tolerance, with ISRTs returning to baseline within 6 days of termination. A second set of experiments determined whether tolerance could be studied using a multi-dose method to obtain dose-response data in a single session. A system of multiple pumps allowed testing of three doses of cocaine during a single experimental session. Cocaine dose-response curves obtained from the multi-dose method: (i) did not differ from that obtained from a single-dose method; (ii) were reproducible; and (iii) were shifted to the right by Schering 23390. Rats were then subjected to a 7-day chronic regimen of infused cocaine (20 mg/kg per 8 h) or infused saline. At the end of this chronic cocaine period, they were tested with the multi-dose method. Chronic cocaine, as compared to chronic saline, shifted the cocaine dose-response curve to the right, indicating that the multi-dose method can be successfully applied to demonstrate tolerance to the effects of cocaine in a self-administration paradigm.

Animals↗
PubMed1993

Relaxation training for NIDDM. Predicting who may benefit.

OBJECTIVE: To examine the benefits of relaxation training for patients with NIDDM and to investigate individual differences that could predict a positive response to relaxation training. RESEARCH DESIGN AND METHODS: Thirty-eight subjects with NIDDM were treated with intensive conventional diabetes therapy after an initial metabolic evaluation and psychological and pharmacological testing. Half were assigned to also receive biofeedback-assisted relaxation training. Treatment effects on GHb levels and glucose tolerance were evaluated after 8 wk. RESULTS: Subjects demonstrated significant improvements in GHb level, but not in glucose tolerance, after 8 wk of intensive conventional treatment. These improvements persisted throughout the follow-up period. However, the group provided with relaxation training did not experience greater improvements on either measure than the group given conventional diabetes treatment only. Within the group that received relaxation training, correlations occurred between the improvements in glucose tolerance after treatment and individual differences in trait anxiety and in the effect of alprazolam on glucose tolerance. Differences in the effects of EPI on glucose tolerance and personality measures of neuroticism and perceived locus of control also appeared to be related to improvements in glucose tolerance after training. CONCLUSIONS: Relaxation training did not confer added benefit over and above that provided by conventional diabetes treatment for patients with NIDDM. Additional research is needed to determine whether the administration of relaxation training to selected patients, especially those who are most responsive to stress, would provide benefits for glucose control that are not achieved by conventional treatment.

Analysis of Variance↗
PubMed1993

Conflicting evidence regarding the efficacy of ondansetron in benzodiazepine withdrawal.

These experiments tested the efficacy of the 5-hydroxytryptamine3 antagonist ondansetron (OND) in reversing various aspects of benzodiazepine withdrawal in rats. Three tests were used in which the benzodiazepine antagonist flumazenil was administered to rats receiving chronic administration of chlordiazepoxide. In one test, the elevated plus-maze, flumazenil produced a reduction in time spent in the open arms of the maze; OND completely reversed this effect of flumazenil in a dose-related fashion. However, OND failed to block the effects of the anxiogenic drug pentylenetetrazole (PTZ) in the elevated plus-maze. In a second test, rats were trained to discriminate PTZ. After chlordiazepoxide, flumazenil substituted for PTZ; OND failed to block flumazenil. In a third test, rats maintained on a chronic base line of chlordiazepoxide were trained to discriminate flumazenil from vehicle. In this discrimination, PTZ substituted for flumazenil, and pentobarbital blocked the flumazenil stimulus; OND, however, failed to block the flumazenil stimulus. In a separate set of experiments, OND also failed to reverse the suppression of responding produced in a conditioned emotional response paradigm. Thus, some data from the elevated plus-maze are consistent with the hypothesis that benzodiazepine withdrawal shares common effects with other stimuli known to be anxiogenic, and that OND blocks this aspect of withdrawal. However, all other data are inconsistent with the hypotheses that OND is anxiolytic or has efficacy in reversing benzodiazepine withdrawal. We suggest that ondansetron is likely to have minimal efficacy in humans for the treatment of sedative-hypnotic withdrawal.

Animals↗
PubMed1992

Neurochemical changes associated with the action of acute administration of diazepam in reversing the behavioral paradigm conditioned emotional response (CER).

Neurotransmitter turnover of biogenic monoamines (dopamine, norepinephrine, and serotonin) and amino acids (glutamate, aspartate, and gamma-aminobutyric acid) was evaluated in rats exposed to the conditioned emotional response (CER) paradigm in the absence (total suppression) or presence of acute 5 mg/kg i.p. diazepam (which reversed suppression and restored normal responding). Based on previous studies of CER, with controls for shock and stimulus histories, the results with respect to the anxiolytic could be divided into several categories: changes in turnover which are associated only with the CER behavior; changes associated only with the drug, diazepam; changes which augmented the effects of the behavior; or changes which were the reverse of those associated with the behavior. Due to the multitude and complexity of the results, not all observations have clear explanations at this time. However, for the CER behavior per se, it is apparent that a combination of neurotransmitters, including some implications about acetylcholine, act in concert to bring about the behavioral suppression. The action of diazepam is more complex, involving the full spectrum of neurotransmitters to bring about its direct and indirect effects.

Amino Acids↗
PubMed1992

Menstrual cycle effects on caffeine elimination in the human female.

Increases in the levels of sex steroids due to pregnancy or oral contraceptive steroid use are known to decrease significantly the rate at which caffeine is eliminated from the body. An investigation has now been made into whether the changes in sex steroid levels that occur during normal menstrual cycling also affect the rate of caffeine elimination, especially whether hormonal shifts in the luteal phase are associated with slower elimination of caffeine. Repeated 24-hour caffeine elimination studies were conducted during the follicular and luteal phases of the menstrual cycle in 10 healthy women. Comparisons of the follicular and luteal phases revealed that systemic clearance of caffeine was slower in the luteal phase, although the t1/2 did not differ. The slowing effect was related to the proximity to onset of menstruation and to levels of progesterone. The evidence suggests that caffeine elimination may be slowed in the late luteal phase, prior to the onset of menstruation. Such a reduction would lead to increased accumulation of caffeine with repeated self-administration during the day, but the effect may be too small to be of clinical significance in the majority of women.

Administration, Oral↗
PubMed1992

Failure of ondansetron to block the discriminative or reinforcing stimulus effects of cocaine in the rat.

Ondansetron (GR38032F), a serotonin 5HT3 antagonist, is active in numerous behavioral paradigms and neurochemical systems. Since 5HT3 antagonists have been suggested as therapeutic agents for the treatment of drug abuse, the action of ondansetron on cocaine drug discrimination and self-administration paradigms in rats was investigated. Doses of ondansetron (0.001 - 1.0 mg/kg) had no effect on the discriminative stimulus properties of 10 mg/kg cocaine. In contrast SCH23390, a dopamine D1 antagonist known to block cocaine discrimination, acted as previously reported. Ondansetron did not augment the effects of SCH23390, but at higher doses, combinations of ondansetron and SCH23390 produced disruption of lever pressing in the presence of cocaine. Ondansetron (0.001-1.0 mg/kg) had no effect on the self-administration of various doses of cocaine, nor did it have any effect on reacquisition of cocaine self-administration in animals with a history of active administration followed by a period of abstinence. As before, SCH23390, known to block cocaine self-administration, acted as previously reported. Although other 5HT antagonists may prove to be efficacious in cocaine abuse, ondansetron appears unlikely to alter the subjective or rewarding stimulus properties of cocaine.

Animals↗
PubMed1992

Respiratory sinus arrhythmia and cardiovascular responses to stress.

The parasympathetic nervous system provides mechanisms that could attenuate sympathetically mediated heart rate stress responses and might have even more general antagonistic actions on stress reactivity. Individuals characterized by higher levels of parasympathetic tone might, through such mechanisms, be less reactive when stimuli elicit sympathetically mediated responses. Respiratory sinus arrhythmia (RSA) is considered to be a noninvasive index of cardiac parasympathetic (vagal) tone. The present study investigated whether individual differences in RSA level at rest could predict variations among individuals in the magnitude of cardiovascular responses to psychological stress. None of the measures of resting respiratory sinus arrhythmia, derived from spectral analysis of beat-to-beat changes in resting heart rate, predicted the observed variations in cardiovascular task reactivity. However, scores reflecting respiratory sinus arrhythmia as the percentage of total heart rate variability (RSAnorm) were negatively correlated with blood pressure levels, both at rest and during the task. Furthermore, subjects with higher scores for RSAnorm demonstrated a faster adaptation of heart rate responses during stress, which suggests the development of parasympathetic antagonism to ongoing sympathetic arousal. Although a simple relationship between respiratory sinus arrhythmia and reactivity was not observed, these results encourage further investigation of RSA measures as psychophysiological indices of individual differences in parasympathetic (vagal) cardiac tone, or perhaps of general parasympathetic/sympathetic balance, which could modulate the expression of potentially pathogenic stress responses.

Adaptation, Physiological↗
PubMed1992

Accentuated vagal antagonism of beta-adrenergic effects on ventricular repolarization. Evidence of weaker antagonism in hostile type A men.

BACKGROUND: Prior research has suggested a weaker parasympathetic antagonism of sympathetic effects on the heart in type A (coronary-prone) men. To confirm this phenomenon and extend our understanding of it, we investigated the effects of prior muscarinic blockade on the electrocardiogram T wave and other cardiovascular and neuroendocrine responses to isoproterenol in type A and type B (non-coronary-prone) men. METHODS AND RESULTS: Responses to two 5-minute intravenous isoproterenol infusions (0.01 micrograms/kg/min and 0.02 micrograms/kg/min) were evaluated in six type A and six type B men after pretreatment with either dextrose placebo or atropine (1.2 mg). Atropine significantly potentiated T wave attenuation in the recovery period after isoproterenol infusion (0.30 +/- 0.07 mV) compared with placebo (0.54 +/- 0.09 mV, p less than 0.001). Atropine also potentiated the heart rate increase to isoproterenol (39 +/- 3 beats per minute versus 20 +/- 2 beats per minute after placebo). Atropine enhanced decreases in systolic, diastolic, and mean arterial pressures as well as pulse pressure to isoproterenol. Atropine enhancement of many of these responses was increased among subjects with high scores on various hostility/anger scales. Isoproterenol alone produced greater T wave attenuation in type A than in type B men. However, atropine enhancement of T wave attenuation and blood pressure falls by isoproterenol was present only in type B men. CONCLUSIONS: These findings indicate that there is accentuated parasympathetic antagonism of T wave attenuation and blood pressure responses induced by beta-adrenergic stimulation. Relative weakness of this antagonism of sympathetic effects on the heart in hostile type A individuals may contribute to their higher coronary disease risk.

Adult↗
PubMed1989

Patterns of cardiovascular responses to stress as a function of race and parental hypertension in men.

This study investigated cardiovascular responses to two stressors known to elicit either beta-adrenergic (mental arithmetic) or alpha-adrenergic (forehead cold pressor) reactivity in Black and White men. Participants in each group were selected for presence or absence of parental hypertension. Based on previous research, Blacks were expected to show smaller cardiovascular responses to the beta-adrenergic mental arithmetic task and greater responses to the alpha-adrenergic cold pressor relative to the Whites. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate, forearm blood flow, and forearm vascular resistance were assessed during a resting baseline, a prestress period, and during and after each experimental procedure. Unlike previous findings, no significant racial differences in cardiovascular responses were found during either task. However, Black participants had significantly higher SBP and DBP levels throughout the cold pressor periods. Parental history did not significantly influence cardiovascular responses in either group. The results are discussed in relation to previous research on racial differences in stress reactivity and their implications for future research.

Adrenergic Fibers↗
PubMed1989

Race, parental history of hypertension, and patterns of cardiovascular reactivity in women.

This study examined the interaction of race and parental history of hypertension on patterns of cardiovascular responses among women. Two stressors were used that produce different patterns of cardiovascular reactivity: mental arithmetic, primarily a beta-adrenergic stimulus, and the cold face stimulus, which evokes alpha-adrenergic (i.e. vascular) activity. Systolic and diastolic blood pressure, heart rate, forearm blood flow, and forearm vascular resistance were assessed before, during, and after arithmetic and cold face stimulus. Both tasks produced the expected patterns of cardiovascular adjustment, although no Black-White differences occurred during arithmetic. However, Black subjects did show a slower recovery of diastolic blood pressure following arithmetic. The cold face stimulus produced significantly greater changes in systolic blood pressure in the Black than in the White women. Parental history of hypertension did not relate significantly to reactivity. The results provide limited support for the idea that Black females exhibit a greater pressor response than White females to a stimulus that produces primarily vascular rather than cardiac changes. These findings are discussed in relation to previous findings with males and with respect to their implications for the role of reactivity in Black-White differences in hypertension prevalence.

Adolescent↗
PubMed1988

Diminished regulation of mesolimbic dopaminergic activity in rat after chronic inorganic lead exposure.

Previous studies in this laboratory have indicated that chronic lead (Pb) exposure during development induces a neurotoxicity in dopamine (DA) neurons that is primarily presynaptic in nature and at least partially related to altered regulation of DA synthesis. A primary form of DA synthesis regulation is the inhibition exerted on synaptic tyrosine hydroxylase activity via dopaminergic autoreceptors. This study assessed the functional status of this mechanism in Pb-exposed rats employing a pharmacological model. At parturition dams received 0.2% Pb acetate (1090 ppm) in the drinking water while control dams received distilled water. Offspring were weaned to and maintained on the same solution given their dams until termination at 125 days. Rats were given saline or 6,7-dihydroxy-2-dimethylaminotetralin (TL-99, 2.5-20 mg/kg ip) 40 min before termination followed 10 min later by 750 mg/kg ip of gamma-butyrolactone (GBL) or saline. The ability of TL-99 to prevent the GBL-induced increase in DA content was significantly diminished in nucleus accumbens (NAc) of exposed rats compared to controls, indicating that chronic Pb impairs receptor-mediated regulation of DA synthesis in mesolimbic neurons. No effect of Pb was observed in caudate-putamen. In animals receiving only saline injections concentrations of the DA metabolites, homovanillic acid and dihydroxyphenylacetic acid, were significantly decreased by Pb in the range of 17-31% and 12-24%, respectively. DA content was also significantly diminished by Pb in ventral tegmental area of these latter groups. These findings suggest that chronic Pb has multiple actions on central nervous system dopaminergic neurons consisting of an impaired regulation of DA synthesis that is apparently independent of a decrease in DA release.

4-Butyrolactone↗
PubMed1988

Racial differences in cardiovascular reactivity to mental arithmetic.

One hypothesized mechanism for the higher rates and greater severity of essential hypertension among blacks is that this group is particularly susceptible to stress-induced beta-adrenergically mediated cardiovascular hyperreactivity. In this study, we compared the cardiovascular responses to mental arithmetic in 20 white and 17 black, young, normotensive males. Contrary to expectations, the black subjects exhibited significantly smaller changes in heart rate, and systolic and diastolic blood pressure. These findings suggest that cardiovascular reactivity to a mental stressor known to produce beta-adrenergically mediated responses may be lower in some normotensive blacks compared to their white counterparts.

Black or African American↗