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Biomedical subjects

D E Fleming

Publications and source records attributed to D E Fleming.

At least 37 records · Page 2Linked to original sources

Relationships between sexual activity, plasma testosterone, and the volume of the sexually dimorphic nucleus of the preoptic area in prenatally stressed and non-stressed rats.

The sexually dimorphic nucleus of the preoptic area (SDN-POA) has recently been shown to be reduced in cross-sectional area in prenatally stressed male rats. As masculine copulatory behavior is also reduced in prenatally stressed animals, the present study was designed to test a possible relationship between the entire volume of the SDN-POA and masculine sexual activity in both prenatally stressed and control adult male rats. We report here that prenatally stressed adult males have significantly reduced SDN-POA volumes, reduced levels of sexual activity and lower plasma testosterone levels as compared to control animals. Additionally, however, a strong positive relationship was demonstrated between SDN-POA volume and sexual activity in both stressed and control animals. SDN-POA volumes of sexually active animals from stressed and control groups are approximately equal. SDN-POA volumes of sexually non-active animals are also equal and are about two times smaller than those of sexually active animals, either stressed or control. Similar correlations are reported between SDN-POA volume and testosterone level, and between testosterone level and sexual activity. It is concluded that (1) SDN-POA volume is predictive of sexual activity in both stressed and control male rats, (2) there is a relationship between SDN-POA volume and plasma testosterone level, and (3) the SDN-POA likely has multiple roles in the circuitry underlying masculine reproductive processes and hormone regulation.

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Effects of prenatal stress on sexually dimorphic asymmetries in the cerebral cortex of the male rat.

Diamond and collaborators have reported sexual dimorphic right greater than left thickness asymmetries in the cerebral cortices of male Long-Evans rats. In the present work we report that normal Sprague-Dawley males show a similar cortical asymmetry. On the other hand, Sprague-Dawley males whose mothers were subjected to treatments of prenatal stress three times daily during the third trimester of gestation showed a nonsignificant left greater than right pattern in the same cortical areas--a pattern characteristic of the female cortex. These results are consistent with other findings from our laboratory wherein we have recently shown that prenatal stress during the third trimester of gestation demasculinizes sexually dimorphic regions of the preoptic hypothalamus in male rats. It is concluded that stress mediated changes in the prenatal environment can have a profound effect on the developmental processes which shape the morphology of sexually dimorphic regions of the brain in male offspring. Normal male anatomy is biased in the direction of a feminine structure. Such an anatomical picture is consistent with demasculinized and feminized behavior patterns exhibited by male offspring of prenatally stressed dams.

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Effects of prenatal stress on differentiation of the sexually dimorphic nucleus of the preoptic area (SDN-POA) of the rat brain.

The present study was designed to determine the effects of prenatal malnutrition or environmental stress on the development of the sexually dimorphic nucleus of the preoptic area (SDN-POA). Pregnant rats were divided into a control group and two treatment groups (immobilization-illumination-heat or environmental stress, and nutritional stress). The two forms of stress were administered during the third trimester of gestation (days 14-20). Male and female offspring were sacrificed at birth, 20, and 60 days postnatally. The cross-sectional area of the SDN-POA was identified under light microscopy and was measured. The data confirm previous studies by showing a significant sex difference in the SDN-POA between control male and female rats. Prenatally stressed males sacrificed 20 and 60 days after birth showed SDN-POA areas 50% smaller than the nuclear areas of control males. The size of the SDN-POA of female offspring, however, was not significantly altered by prenatal treatments.

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The effects of frontal lesions on brain hypersynchronous bursting and behavioral activity.

Photically evoked after-discharge (PhAD) bursting was examined in lightly restrained albino rats following frontal and mid-cortical lesions. The initial effect of dorsal frontal lesions was to significantly suppress PhAD occurrence. Spontaneous activity as measured on an open-field arena was examined as a second variable. Frontally lesioned animals were significantly more active than mid-cortically lesioned and non-lesioned control animals in the initial stages of behavioral testing. These results indicate that the frontal cortex has an inhibitory influence on reticular formation (rf) arousal mechanisms which are responsible for behavioral arousal and the modulation of hypersynchronous burst-like phenomena occurring at the level of the cortex.

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Thalamocortical coupling and component properties of visually evoked afterdischarge.

Dorsal lateral geniculate nucleus (dLGN) multiple-unit activity (MUA) and single visual evoked responses (VER) followed by afterdischarge (AD) were examined in lightly restrained albino rats. It was found that VER AD spike components are initially quite prominent, exceeding at times the amplitude of the broad surface negative wave components. As VER AD progresses toward termination spike amplitude systematically declines. Wave amplitude, however, remains relatively stable until spike components disappear. Averaged dLGN MUA and VER AD responses to photic stimuli suggest the existence of a precise time-locked relationship between peak dLGN MUA and VER AD spike components. It is proposed that thalamic and cortical mechanisms sustaining VER AD bursting might be operative during sensory information ;processing, serving to sustain neural activity functionally related to stimulus input.

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Visual cortical hypersynchronous bursting as an index of shifts in behavioral state.

Photically evoked after-discharge (PhAD) bursting was examined in lightly restrained albino rats during habituation of a leg flexion response. The initial effect of iterative footshock (200 trials, 0.17 mA, 2.5 msec duration, separated by 1.0 sec) was to block PhAD bursting. As response habituation developed PhAD reappeared at reduced levels, subsequently returning to control levels as habituation progressed and became complete. The number of spindles per PhAD burst was suppressed for a brief period which coincided with response sensitization. These results are interpreted as demonstrating that phasic shifts in behavioral state are reflected by PhAD parameters. In addition, the possible relationship between cortical information processing and PhAD bursting is discussed with reference to putative neural mechanisms involved.

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Differential effects of convulsants on visually evoked responses in the albino rat.

Visually evoked responses (VERs) were recorded from primary visual cortex in unanesthetized albino rats during pharmacological modulation by one of the following convulsant agents: Physostigmine, picrotoxin, strychnine and Metrazol. The data were analyzed in terms of effects on VER components. The rat VER consists of six distinct waves constituted by three positive peaks (P1--P3) and three negative peaks (N1--N3). Results indicate a differential convulsant action on VER components. The administration of picrotoxin, resulted in a suppression of the peak amplitude of P1--N1 and delayed peak latencies of all components. Strychnine reliably shortened P1, N1 and P2 peak latencies, significantly increased N3 peak latency and only suppressed P3--N3 amplitude. Physostigmine essentially suppressed all component amplitudes but only increased peak latencies for P2 and P3 components. Metrazol, in general, was found to be relatively ineffective in the alteration of any VER component in a systematic manner. The data are discussed in terms of differential modes of convulsant action on the visual system. The results are likewise discussed with respect to their implications for convulsant modulation of photically evoked after-discharges.

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Pharmacological suppression of photically evoked after-discharges in rats: incremental dose, hippocampal EEG and behavioral activity correlates.

In subjects lightly restrained (Experiment I) pharmacological arousal via pilocarpine, physostigmine, or amphetamine administration, as compared to saline and methyl atropine treated controls, suppressed photically evoked after-discharge (PhAD) activity in visual cortex, while concomitantly inducing rhythmical slow-wave activity (RSA) in dorsal hippocampus. Incremental doses of amphetamine and pilocarpine correspondingly suppressed PhAD parameters in a dose-response fashion. While physostigmine treatment resulted in significant PhAD suppression, this effect could not be quantified in a dose-response manner. Incrementally increased cholinergic blockade via atropine administration also suppressed PhAD bursting yet simultaneously induced large amplitude irregular slow-wave activity (LIA) in dorsal hippocampus. When tested under identical conditions but in an unrestrained environment (Experiment II) PhADs were similarly suppressed with the concomitant induction of hippocampal patterns as specified in Experiment I; however, general ambulatory activity (grid-crossing) was differentially affected by the drugs. Amphetamine and atropine markedly enhanced while pilocarpine and physostigmine suppressed such activity. In both experiments, previously established PhAD-movement, PhAD-RSA-LIA, and RSA-LIA-movement relationships, occurring as hypothesized in amphetamine, methyl atropine, and saline treated animals, did not remain fully intact during cholinergic alteration.

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Metrazol potentiated after-discharges: dose-response relationships and effects of selective lesions.

In Experiment 1 the dose-response effects of pentylentetrazol (Metrazol) on photically evoked after-discharge (PhAD) parameters were examined. Metrazol potentiated PhAD activity by affecting all measured parameters - PhAD frequency, amplitude, burst duration and spindle composition - in particular PhAD burt duration and spindle composition. A mimimum effective dose of 10 mg/Kg of Metrazol was required for some statistically reliable potentiation. Metrazol dosage levels of 20 and 25 mg/Kg induced lengthy bouts of EEG spindling and spiking as well as near maximized PhAD component augmentation. In Experiment 2 stereotaxically oriented knife-cuts isolated the thalamus from cortical and/or midbrain and brainstem input. Such lesions did not block the capacity of Metrazol to potentiate PhADs, although the lesions altered evoked activity. These findings are discussed in terms of the current thought of Metrazol action and thalamic mechanisms in the control of after-discharge activity.

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