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Biomedical subjects

J D Lane

Publications and source records attributed to J D Lane.

At least 19 recordsLinked to original sources

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

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

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

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

Carbonic anhydrase activity in myelin fractions from rat optic nerves.

The carbonic anhydrase activity of myelin fractions isolated from the optic nerves of adult and immature (20-day-old) rats was examined. The specific activity in both total homogenate and myelin fractions was about 2-fold higher in adult than in immature animals and at both ages, the activity in the homogenate was higher than in myelin. After subfractionation by zonal gradient centrifugation, it was shown that carbonic anhydrase activity was greatest in the heaviest myelin particles at both ages. These data are consistent with the hypothesis that a small proportion of the total enzyme activity is localised in myelin.

Aging

The fluorescence scanning of microgels stained for glycoproteins with fluorescein isothiocyanate-labelled concanavalin A.

A technique is presented which allows one to label and quantitate glycoproteins. Small amounts of protein from biological samples (0.5-2.5 microgram for mixtures and less for individual proteins) are separated by sodium dodecyl sulfate gel electrophoresis on 1-30% polyacrylamide gradient microgels. The gels are stained with Co-omassie Brillant Blue R250 to evaluate relative migration or fixed in 2-propanol/acetic acid and stained with fluorescein isothiocyanate-labelled concanavalin A. The microgels are then scanned using a fluorescence microscope controlled by a computer, although simpler configurations are possible. Standards of known carbohydrate composition (e.g., glucose oxidase) are used for comparative purposes. Glycoproteins in the order of 5-30 ng protein (or 1-5 ng carbohydrate) can be detected without difficulty. This technique may prove valuable in evaluating glycoproteins when the available material is limited.

Animals