Electrophysiological and biochemical responses of noradrenergic neurons to a non-amphetamine CNS stimulant

Amfonelic acid (AFA), a potent non-amphetamine CNS stimulant, has been shown previously to have marked effects on dopamine (DA) metabolism and DA neuronal activity, but no effect on norepinephrine (NE) metabolism. AFA is known to inhibit the NE neuronal uptake mechanism. Other NE uptake inhibitors, such as desipramine (DMI), have been shown to decrease the firing rate of NE-containing locus coeruleus (LC) neurons. The purpose of the present study was to compare the actions of AFA and DMI electrophysiologically on LC neurons, and biochemically on NE metabolism in whg rate, with DMI being more potent. Brain NE metabolism was not influenced by either AFA or DMI at doses considerably higher than those which were effective in reducing NE neuronal impulse flow. Thus, NE uptake inhibition coupled with a decrease in impulse flow results in no net change in NE metabolite formation. The effects of AFA on LC unit activity do not seem to be due to its marked effects on brain DA, since DA receptor blockade with haloperidol had little effect on LC unit responsiveness to AFA (or amphetamine). Whereas AFA has dramatic effects on DA metabolism via enhanced release per impulse, the drug has minimal effects on NE metabolism, and this specificity of action may be related to differences in NE and DA transmitter storage mechanisms. It is concluded that the effects of AFA on NE neuronal firing rate are likely due to the drug's DMI-like action and not to enhanced NE release per impulse.     

Standardization of tissue culture conditions for spontaneous thymidine-2-14C incorporation by unstimulated normal human peripheral lymphocytes: circadian rhythm of DNA synthesis.

The rate of DNA synthesis by human lymphocytes was studied in vitro by measuring unstimulated thymidine-2-14C incorporation (spontaneous lymphocyte blastogenesis; SLB). Freezing lymphocytes and extracting DNA after thawing did not alter the radioactive label count rate and was as efficient as extracting DNA immediately after culture. Omission of fetal calf serum also did not alter the rate of DNA synthesis. Standards established as optimal for studies of SLB were: cell concentration, 1.0 times 10(6)/ml/tube; 14C-TdR concentration, 0.4 mjCi/tube; duration of incubation, 8 hr. In sets of identical samples obtained by specimen division, the variation in counts was 6%. To achieve reproducibility of results; it was essential to count the lymphocytes, and then to ensure that each tube contained almost precisely known numbers of cells. Diurnal variations in the rate of DNA synthesis by circulating lymphocytes of healthy men were measured in vitro by SLB at 2-hr intervals for 24 hr. Leukocyte counts, hematocrit, hemoglobin, plasma cortisol, and body temperature were monitored concurrently. The DNA synthesis rate varied in a 24-hr cycle with peaks at 10 A.M. and 11:00 P.M.., depressions at 4 A.M. and 4 P.M. The rate was correlated with body temperature and hematocrit level, and inversely related to the absolute eosinophil count.     

Computer analyses of auditory evoked cortical potentials in schizophrenic subjects.

Averaged cortical evoked potentials from single clicks were recorded from 51 patients and controls. The patient group consisted of 40 subjects with a diagnosis of 'nuclear' schizophrenia, and 11 subjects with diagnoses including mania, anxiety neurosis and personality disorder. Changes in auditory evoked cortical responses (AECR's) were most marked in clinically stable, dysphoric, chronic schizophrenics. These subjects showed reproducible, low amplitude, 'untidy' responses in which the amplitude of the primary peak was lower than the amplitude of later peaks. Chronic schizophrenics who were rated as being depressed, showed a more 'normal' AECR. AECR changes during the memorising of nonsense syllables demonstrated a functional separation between early and later peaks of the AECR. It was postulated that the AECR changes in schizophrenia and during memorising result from pathological patterns of cortical desynchronisation produced by altered mid-brain activity different from that of anxious arousal, and that the clinical 'steady-state' of chronic schizophrenia is reflected in the 'steady-state' desynchronisation changes in the AECR.     

Anatomic and pharmacologic differences between two types of aversive midbrain stimulation.

Chronic stimulating electrodes were implanted into two separate midbrain sites in rats. One site was the dorsal central gray area (DCG), where electrical stimulation produced frantic, escape-seeking behavior which grossly appeared fear-like and/or pain-like. The other site was in the ventral reticular formation (VRF), where stimulation produced a stereotyped circling response. Stimulation at both sites was aversive in that these animals would bar press for escape in a decremental bar-pressing paradigm. In this paradigm, each bar press decremented the current by five per cent of the initial current level. Following the acquisition of stable baseline decremental bar-pressing performance, animals were given injections of either the serotonin-depleting drug, para-chlorophenylalanine (PCPA), or the catecholamine-depleting drug, alpha-methyl-para-tyrosine (AMPT). Control animals received normal saline. Compared to saline control animals, PCPA-injected DCG-stimulated animals showed a marked increase in decremental bar pressing, whereas VRF-stimulated animals showed no change. AMPT-injected VRF-stimulated animals showed a marked decrease in decremental bar pressing, but the DCG-stimulated animals were not affected. These results suggest that escape behavior from electrical stimulation of midbrain sites is mediated by more than one neural system.     

The role of time and size in ontogenetic allometry: I. Review

Several interconnected issues are a part of most studies of ontogenetic allometry, the relationship between size and shape during growth. One issue is the choice of a model, either linear or one of a series of nonlinear models that have been proposed in the literature. The independent variable, against which growth is assessed, can be a measure of time, e.g., age or a measure of size, e.g., weight. These categories of independent variables have become confused with Medawar's (1945) classification of allometric studies as empirical or deductive. Medawar's distinction may be less useful than Tukey's (1980) between exploratory and confirmatory studies. The "correct" choice for some of these options will be a function of the data set being analyzed. However, an understanding of the implications of these issues is necessary to make the correct choices.