Biomedical subjects

J L Muir

Publications and source records attributed to J L Muir.

48 records · Page 3Linked to original sources

PubMed1992

Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms.

The behavioral effects of GABAergic manipulation of the basal forebrain were investigated using two behavioral tasks, which previous studies have shown to yield dissociable effects following quisqualate-induced lesions of the basal forebrain: a five-choice serial reaction time task, involving approaching the location of a brief visual stimulus that is associated with reward; and a conditional visual discrimination task, requiring retrieval of information about a discriminative stimulus that stays constant over time. Following acquisition of the tasks, chronic guide cannulae were stereotaxically implanted into the basal forebrain. Those animals trained on the conditional visual discrimination task showed a dose-dependent reduction in choice accuracy and a lengthening of latency to respond correctly to the visual stimulus following administration of the GABA-A agonist, muscimol (1, 2, 3 ng/microliters/hem). While certain of these deficits, for example response latency, could be restored to control levels by co-administration of the GABA-A antagonist, bicuculline, none of the behavioural impairments could be significantly attenuated by systemic by systemic co-administration of the cholinesterase inhibitor, physostigmine (0.05, 0.1, 0.2 mg/kg, IP). Similarly, a dose dependent effect of muscimol (1, 1.5, 2 ng/microliters/hem) on choice accuracy and correct response latency was observed on performance of the five-choice attentional task. However, in contrast to the conditional task, significant attenuation of the impairment in choice accuracy was obtained following administration of physostigmine (0.05 and 0.1 mg/kg). Attenuation of muscimol-induced deficits by administration of bicuculline was also observed. It is therefore evident that although manipulation of GABAergic activity in the region of the basal forebrain produces profound deficits in different tasks of cognitive function, only some of these may be due to modulation of the magnocellular cholinergic projection to the neocortex.

Animals↗

PubMed1992

A specific form of cognitive rigidity following excitotoxic lesions of the basal forebrain in marmosets.

The effects of N-methyl-D-aspartate-induced lesions of the basal forebrain were studied on performance of a series of visual discrimination tests that examined a range of cognitive functions in the marmoset. These included the ability to attend to the various dimensional properties of stimuli and to use just one of these properties in order to solve a discrimination (intra-dimensional shift); to switch attention from one dimension to another (extra-dimensional shift); to learn the reinforcement value of specific exemplars within a dimension (new learning); and to relearn their reinforcement value following reversal of the reward contingencies (serial reversals). Lesions of the basal forebrain did not impair the ability either to attend selectively to the dimensional properties of the stimuli or to switch attention from one dimension to the other. However, the lesion did affect various aspects of associative learning including a transient impairment of new learning and a marked disruption of serial reversal learning. The reversal deficit could be characterised as a tendency to perseverate on the previously correct stimulus and as a failure to to show the formation of a reversal learning set. In addition, the lesion prevented disruption of performance of a well-learned discrimination when novel exemplars from the irrelevant dimension were introduced (probe test). It is suggested that the functional effects of the basal forebrain lesion reflect impaired learning of stimulus-reward associations and behavioural rigidity. The finding, however, that there was no effect of the lesion on attentional set-shifting suggests that any loss of inhibitory control was specific to the level of stimulus-response or stimulus-reward associations, inhibitory control at the level of attentional selection remaining intact. The similarity of the effects of damage to the basal forebrain to those seen following damage to the orbitofrontal cortex and the amygdala are discussed in the context of the close anatomical and functional relationships that exist among these three structures.

Animals↗

PubMed1992

Prenatal exposure to predictable and unpredictable novelty stress and oxytocin treatment affects offspring development and behavior in rats.

Prenatal stress in rats usually results in behavioral and developmental changes in offspring. This experiment assessed body weight during the first three weeks postpartum and subsequent behavior of the offspring when tested as adults. Pregnant females allocated to the stress condition were exposed during the third week of pregnancy to either predictable (NOV1) or unpredictable (NOV2) psychological novelty stress. At this time, pregnant rats were also treated with various doses of oxytocin or vehicle solution. The exposure to unpredictable novelty stress during the third week of pregnancy resulted in pups which were significantly heavier at birth than either control animals or those which had received predictable exposure to the novelty stress. In contrast, oxytocin treatment appeared to lower body weight of offspring compared to control animals. This effect was observed right up until Day 21 postpartum for animals exposed to the larger dose (11.6 I.U.) of oxytocin. When tested as adults, NOV1 and NOV2 offspring were found to defecate more in the open field setting suggesting the they were more emotional than control animals. It was concluded that psychological stress during pregnancy has a subtle effect on development and subsequent effects on later emotionality of the offspring when tested as adults.

Adrenocorticotropic Hormone↗

PubMed1989

Psychological stress and administered oxytocin during pregnancy: effect corticosterone and prolactin response in lactating rats.

Recent evidence suggests that oxytocin modulates both ACTH and prolactin secretion. The present study was designed to investigate the possible role of oxytocin in the corticosterone and prolactin response to predictable and unpredictable novelty stress. These responses were examined in lactating females (Day 6 and Day 21 postpartum) which had received stress and oxytocin treatment during pregnancy. The results demonstrated that exposure to the novelty stressors during pregnancy resulted in a significant elevation in corticosterone levels of lactating females on Day 6 postpartum. A similar elevation was also observed on Day 21 postpartum for the unpredictable condition. Oxytocin treatment did not, however, significantly affect the corticosterone response to the psychological stressor. Furthermore, prolactin levels were not significantly affected on either Day 6 or Day 21 postpartum by either novelty stress or oxytocin treatment administered during pregnancy. It was suggested that the sustained elevation in corticosterone levels obtained following unpredictable exposure to the stressor had important implications for the lactation process.

Animals↗

PubMed1989

Influence of exogenously administered oxytocin on central noradrenaline, dopamine and serotonin levels following psychological stress in nulliparous female rats (Rattus norvegicus).

This study was designed to examine the effects of psychological stress and oxytocin treatment (5.8 or 11.6 IU/kg) on noradrenaline, dopamine and serotonin levels in the hypothalamus, hippocampus and brainstem. Results indicated that repeated exposure to the novelty stressor resulted in amine levels which did not significantly differ from those of control levels. In contrast, oxytocin treatment produced a significant elevation in serotonin levels in each of the three brain regions examined, while the effects for dopamine were confined to the hypothalamus. Furthermore, when oxytocin was administered immediately prior to unpredictable exposure to the novelty stressor, a significant increase in levels of noradrenaline in the hypothalamus and serotonin in the hippocampus and brainstem were observed. These results suggest that oxytocin may play an important role in modulating monoaminergic activity which is also apparent when the animal is exposed to a psychological stressor.

Animals↗

PubMed1989

Psychological stress and oxytocin treatment during pregnancy affect central norepinephrine, dopamine and serotonin in lactating rats.

The aim of these experiments was to investigate the effects of psychological stress and oxytocin treatment on levels of norepinephrine, dopamine and serotonin in the hypothalamus, hippocampus, striatum, midbrain and brainstem of lactating females. Stress and oxytocin treatment were applied during the third trimester of pregnancy, and females examined on day 6 and day 21 postpartum. The results indicated that serotonin levels were significantly increased on day 6 following unpredictable novelty stress during pregnancy. Furthermore, a marked reduction in serotonin levels in the hypothalamus, hippocampus, midbrain and brainstem was observed as a result of oxytocin treatment on both Day 6 and Day 21 postpartum. These results are in stark contrast to those obtained for nulliparous females in a previous study and suggest an important distinction between nulliparous and lactating females with respect to the effects of psychological stress and oxytocin treatment on central monoamine levels.

Animals↗

PubMed1988

Influence of exogenously administered oxytocin on the corticosterone and prolactin response to psychological stress.

Prolactin along with corticosterone is a stress responsive hormone. Evidence suggests that oxytocin (OXT) modulates not only ACTH secretion but also prolactin release. The present study was therefore designed to examine the possible role of oxytocin in the corticosterone and prolactin response to predictable and unpredictable novelty stress. Repeated stress and oxytocin treatment produced a substantial increase in corticosterone. A greater increase was obtained for the larger OXT dose (11.6 IU/kg) than for the smaller dose (5.8 IU/kg). In addition, for the smaller oxytocin dose only, unpredictable exposure to the novelty apparatus produced a more substantial increase in corticosterone than predictable exposure to the same stressor. In contrast, oxytocin produced a significant suppression of the prolactin response in all OXT treated animals. No significant interaction between stress and oxytocin was obtained. It was concluded that an important role exists for oxytocin in the modulation of both corticosterone and prolactin secretion.

11-Hydroxycorticosteroids↗

PubMed1987

Time course of the corticosterone and prolactin response following predictable and unpredictable novelty stress in Rattus norvegicus.

Marked changes in corticosterone and prolactin levels are observed following repeated psychological stress. Furthermore, these responses appear to be affected by the pattern of exposure to the stressor. The present study examined the time course of the corticosterone and prolactin responses following predictable and unpredictable novelty stress. On the fifth day of stress treatment, predictable and unpredictable exposure to the novelty apparatus produced a peak corticosterone response after 15 min of stress treatment. Although corticosterone levels began to decline for both these treatment groups after 15 min, substantially higher levels were observed following unpredictable stress. The steroid levels of animals receiving unpredictable stress treatment continued to be significantly higher than those receiving predictable stress until 30 min post-stress. Predictable stress failed to significantly alter prolactin levels from controls at any of the time points examined. However, unpredictable exposure to the novel apparatus produced high baseline prolactin levels and a subsequent suppression of this response during exposure to the stressor. It was concluded that the differences obtained between animals receiving predictable and unpredictable exposure to novelty reflect a difference in the magnitude of these responses rather than a difference in their temporal pattern.

Animals↗

PubMed1986

Corticosterone and prolactin responses to predictable and unpredictable novelty stress in rats.

Prolactin along with corticosterone is a stress responsive hormone. The present study examined the effect of predictable and unpredictable psychological stress on corticosterone and prolactin secretion. Repeated unpredictable exposure to the novelty cage produced a more substantial increase in the level of corticosterone than predictable exposure to the same novelty apparatus. In contrast, predictable novelty stress induced a more substantial elevation in prolactin levels than unpredictable stress. Furthermore, it was observed that both corticosterone and prolactin returned to control levels 30 minutes after the fifth exposure to the novelty cage. It was concluded that the pattern of exposure to novelty is an important paradigm which effects the magnitude of hormonal responding. An important relationship between corticosterone release and prolactin secretion is also indicated.

Animals↗

PubMed1986

A possible role for oxytocin in the response to a psychological stressor.

Recent evidence suggests that oxytocin (OXT) potentiates corticotropin releasing factor-induced secretion of ACTH. The present study was therefore designed to investigate the possible role of oxytocin in the response to predictable and unpredictable novelty stress. The results clearly demonstrate that oxytocin produced a significant increase in corticosterone in all OXT treated animals. Repeated unpredictable exposure also produced a more substantial increase in corticosterone than predictable exposure to the same stressor. However, a significant interaction between stress and oxytocin was not obtained. It was concluded that whereas corticosterone is released in response to most types of stress, administration of oxytocin does not potentiate the corticosterone response to psychological stress.

11-Hydroxycorticosteroids↗

PubMedDate not supplied

Decline in visual attention and spatial memory in aged rats.

The present study was a longitudinal study of age-related changes in performance of the 5-choice serial reaction time task, a test of visual attention. Following acquisition of the task, animals were tested on two occasions on their ability to perform the 5-choice task. In Test 1 (Young: 7 months; Aged: 13-14 months) no age-related effects on baseline performance were revealed. However, increasing the attentional load of the task revealed an impairment in choice accuracy by animals of the Aged group. In Test 2 (Young: 10-11 months; Aged 23-24 months), animals of the Aged group were significantly impaired on the baseline schedule of the task compared to the Young group. The deficit in accuracy on the task could be improved in the Aged animals by decreasing the attentional load. The results of the present study suggest a deficit in attentional function as a result of the aging process, markedly similar to that observed following lesions of the basalo-cortical cholinergic system.

Aging↗

PubMedDate not supplied

The cerebral cortex of the rat and visual attentional function: dissociable effects of mediofrontal, cingulate, anterior dorsolateral, and parietal cortex lesions on a five-choice serial reaction time task.

Dissociable effects of bilateral excitotoxic lesions of different regions of the rat neocortex, including medial prefrontal and anterior cingulate cortices, were investigated in a five-choice serial reaction time task that provides several indices of the accuracy and speed of attentional function. Whereas medial prefrontal cortical lesions impaired performance of the task as revealed by a reduction in choice accuracy, an increase in the latency to respond correctly to the visual target and enhanced perseverative responding, lesions of the anterior cingulate cortex specifically increased premature responding. By contrast, lateral frontal cortical lesions did not significantly disrupt baseline performance of the task, but rather increased the latency to respond correctly to the visual target during various behavioral manipulations, for example, when the length of the intertrial interval was varied unpredictably and during interpolation of distracting bursts of white noise. Lesions of the parietal cortex failed to disrupt any aspect of task performance investigated. These behavioral effects in the five-choice task were compared with the effect of these same lesions on acquisition and retention of a one-trial passive avoidance task. The main finding from this paradigm was that lesions of the lateral frontal cortex produced a significant disruption to the retention of passive avoidance, which stands in marked contrast to the successful retention observed by animals of the other lesion groups. In addition, this pattern of results reveals that the 'disinhibitory' effect of cingulate cortex lesions are relatively specific to the five-choice attentional task. Finally, the results of the present study are compared with the findings of previous experiments using the five-choice task, which have examined the effect of selective manipulations of the ascending noradrenergic, cholinergic, dopaminergic, and serotonergic projections. In particular, the deficits in attentional function observed following cholinergic lesions of the nucleus basalis magnocellularis appear to be attributable to cholinergic denervation of the medial frontal cortex. These results are discussed in terms of the role of parallel distributed neural systems within the neocortex that mediate continuous attentional performance in the rat.

Acoustic Stimulation↗