Biomedical subjects
Publications and source records attributed to S E Robinson.
Rats treated with L-cocaine HCl exhibited an increase in hippocampal acetylcholine turnover, as measured by a mass fragmentographic technique. Furthermore, the ratio of hippocampal 3-methoxy-4-hydroxyphenylethyleneglycol to norepinephrine increased significantly. Possible mechanisms of the increased cholinergic activity are discussed.
This study examined the effect of fluid percussion head injury on the activity of cholinergic neurons in specific brain areas of the rat 12 min, 4 h and 24 h following injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using a gas chromatographic-mass spectrometric technique. The most striking changes in cholinergic activity were observed in the dorsal pontine tegmentum, where concussive head injury produced an increase in ACh turnover 12 min and 4 h following injury. This area has been previously associated with behavioral changes observed following concussive injury. ACh turnover in the thalamus, a region to which pontine cholinergic neurons project, also tended to increase 4 h following injury. On the other hand, ACh turnover tended to decrease in the amygdala 4 h following injury. Although there were no significant changes in hippocampal ACh content or turnover following injury. ACh content did tend to increase in that brain region 12 min following injury. There were no significant effects of injury on cholinergic neurons in the cingulate/frontal cortex. These changes in cholinergic neuronal activity may contribute to the neurological deficits following concussive injury. In particular, activation of cholinergic neurons in the pontine region may contribute to components of behavioral suppression associated with reversible traumatic unconsciousness. More generalized changes in cholinergic function may lead to the production of more chronic deficits.
Injection of the cholinergic agonist carbachol into the region of cholinergic cell bodies in the basal forebrain decreases the turnover rate of acetylcholine in the cortex of the rat, as measured by a mass fragmentographic technique. Moreover, this treatment has been found to increase the number of working memory errors committed as measured in the 8-arm radial maze. These results suggest an inhibitory cholinergic mechanism on the cell bodies of basal forebrain neurons which may be important in memory and the treatment of Alzheimer's disease.
Intrastriatal injection of soman (14.85 nmol) inhibits cholinesterase (ChE) activity in the striatum with much smaller decreases in ChE activity in other brain areas of the rat. As would be expected, there is a substantial increase in striatal acetylcholine (ACh) content shortly after soman injection. However, this increase is no longer significant 1 h following intrastriatal injection. There is no change in striatal KACh 20 min, 1 h or 24 h following soman injection. ACh content is not affected in the parietal cortex, hippocampus, or medulla/pons following intrastriatal soman injection. However, KACh and/or ACh turnover are reduced in these brain areas following soman injection. There is no consistent effect on dopamine (DA) metabolism in any of the brain areas studied. However, serotonin (5-HT) metabolism appears to be affected in the cortex, hippocampus and medulla/pons following intrastriatal injection of soman. Possible mechanisms of the actions of local injection of soman on brain Ach and 5-HT metabolism are discussed, as well as the differences observed between the effects of local and peripheral administration of soman on DA metabolism in the striatum.
This study examined the effects of scopolamine and fluid percussion traumatic brain injury (TBI) on the activity of cholinergic neurons in specific areas of the rat brain 12 min, 4 h, and 24 h after injury. Acetylcholine (ACh) turnover, used as an index of cholinergic neuronal activity, was determined using gas chromatography-mass fragmentography. Scopolamine pretreatment prevented significant increases in dorsal pontine ACh turnover at 12 min and 4 h after TBI, suggesting that the drug's protective actions against the neurologic deficits following TBI may involve blockade of cholinergic neuronal activation as well as postsynaptic muscarinic blockade. The responses of thalamic, hippocampal, and amygdaloid cholinergic neurons to TBI did not differ substantially in scopolamine-pretreated rats from those studied previously in untreated fluid-percussion-injured rats. However, cholinergic neurons in the cingulate-frontal cortex of rats receiving TBI did respond in a different manner to scopolamine than those of rats receiving sham injury, suggesting a disruption of regulation of cortical cholinergic neurons following this model of TBI.
This study examined the effects of pretreatment with phencyclidine (PCP), a selective N-methyl-D-aspartate (NMDA) antagonist, on behavioral and physiologic responses of the rat to experimental traumatic brain injury (TBI). For the behavioral experiments, rats were administered either saline or PCP (1.0, 2.0, or 4.0 mg/kg, intrapentoneally [IP] 15 min before TBI. Rats were ventilated as necessary following injury. The duration of acute suppression of several reflexes (pinna, corneal, righting, and flexion) and responses (escape, head support, and spontaneous locomotion) was recorded for up to 70 min after trauma. Longer-term behavioral assessments (beam walking, beam balance, inclined plane, ambulatory activity, and body weight) were made for up to 10 days after trauma. PCP did not significantly alter the duration of acute behavioral suppression. At a dosage of 1.0 mg/kg, PCP significantly attenuated all long-term deficits except beam walking. Maximal protection against beam walking deficits was provided by the 4.0 mg/kg dosage of PCP. Sixty-three percent of saline-treated animals died within 10 days after injury. For rats pretreated with 1.0, 2.0, and 4.0 mg/kg of PCP, 40%, 23%, and 33% died, respectively. In physiologic experiments, pretreatment with 4.0 mg/kg of PCP (IP) 15 min before injury did not significantly affect systemic cardiovascular responses, plasma glucose levels, or blood gas levels observed within 30 min after injury. While the possibility of effects mediated by other neurotransmitter systems cannot be excluded, these data suggest that NMDA agonist-receptor interactions contribute to the pathophysiology of brain injury. In addition, neural mechanisms that mediate transient unconsciousness following moderate levels of head injury may differ from mechanisms that mediate more persistent neurologic deficits.
Previous research (Adametz, 1959) has shown that two-step bilateral lesions of the reticular formation in cats produce minimal behavioral disruption compared to one-step bilateral lesions, which produce profound behavioral suppression. We systematically examined alterations in forebrain acetylcholine (ACh) content and neurologic tolerance to one-step and two-step bilateral and unilateral lesions of the pontomesencephalic reticular formation (PMRF) in rats. One-step and two-step bilateral lesions separated by 1 or 5 days produced irreversible bilateral motor dysfunction. Survival after lesioning was 10%, 20%, and 0%, respectively. Unilateral lesion or two-step bilateral lesions separated by 15 or 30 days produced transient (less than 3 days) contralateral motor dysfunction. Survival after lesioning was 90%, 90%, and 100%, respectively. Within 24 h after one-step bilateral lesions, ACh content was significantly decreased bilaterally in thalamus, frontal cortex, amygdala, hippocampus, and basal forebrain. Within 5 days after unilateral lesioning, ACh content was significantly decreased ipsilaterally in the thalamus, amygdala, and hippocampus and had returned to control values by day 10 in the thalamus and hippocampus. The increased neurologic tolerance and recovery of ACh content in two-step bilateral PMRF lesions demonstrate important functional and neurochemical plasticity to brain injury. Although not directly addressing mechanisms of neural plasticity, this research examined possible associations between neurologic tolerance to PMRF lesions and neurochemical markers of forebrain ACh activity.
(+/-)3,4-Methylenedioxymethamphetamine (MDMA) was administered to rats as a single 40 mg/kg injection s.c. or 40 mg/kg s.c. every second day for 4 injections. Sixteen days following the last injection rats were killed. MDMA produced significant depletions of 5-HT and its metabolite 5-HIAA in the hippocampus and the frontal cortex. 5-HT was depleted to 30% of control value in the hippocampus following a single dose. 5-HT levels were not affected in the hypothalamus, suggesting differential effects on brain 5-HT systems. DA levels in the hypothalamus were significantly increased while NE levels in the frontal cortex were decreased to 73% of control following 4 doses of MDMA. MDMA, therefore, produces long-term depletions in 5-HT which suggests that it may act as a neurotoxin at 5-HT neurons in the brain of rats.
As part of the evaluation of a health education campaign about breast disease, consultations for breast problems were monitored in five general practices over an 18-month period in Edinburgh. No increase was found as a result of the campaign, nor was there any increase in the number of biopsies performed. On average, each GP saw 13 women with breast problems each year, a rate of 1.6 per cent; 29 per cent were referred to hospital, regardless of their age. The most common presenting symptom was pain (47 per cent), with 35 per cent complaining of a lump. The reasons for hospital referral are discussed. It is suggested that GPs may refer too many young women to a specialist clinic, although this may be inevitable.
Local injection of the cholinergic agonist carbachol (1-5 nmol) into the ventral lateral periaqueductal gray region of the midbrain produced a dose-dependent bradycardia with minimal effects on blood pressure in the urethane-anesthetized rat. The decrease in heart rate was maximal in the region of the nuclei of the third and fourth cranial nerves. Intravenous injection of carbachol (5 nmol) had little effect on the heart rate. Injection of (-)-nicotine (5 nmol) into this region of the brain produced a slight, but significant, increase in heart rate. Pretreatment with an intracranial injection of atropine greatly reduced the bradycardia response, whereas local injection of mecamylamine or hexamethonium had no effect. The bradycardia resulting from cholinergic stimulation in this area of the brain appears to result from an enhanced vagal influence on the heart, as pretreatment with intravenous atropine methyl nitrate (1 mg/kg) prevented the carbachol-induced bradycardia. The possible physiological significance of this response is discussed.
Rats treated with amphetamine exhibited an increase in hippocampal acetylcholine turnover, as determined by a mass fragmentographic technique. However, administration of amphetamine to rats which had received stereotaxically placed bilateral injections of 6-hydroxydopamine in the ventral noradrenergic bundle 10 days previously did not increase hippocampal acetylcholine turnover. Because the ventral noradrenergic bundle projects to the septal area, it is suggested that amphetamine increases acetylcholine turnover in the hippocampus by an action on noradrenergic neurons in this pathway.
The neurobehavioral responsiveness of two strains of rats, Fischer-344 (CDF) and Sprague-Dawley (CD), to a repeated foot-shock-induced analgesia (FSIA) stress was compared in this study. Rats were either restrained or freely moving during shock presentation (sham controls were exposed to the shock environment only). The foot-shock (15-s, 1.5-mA scrambled electric shock) was observed to induce analgesia in the CDF, but not the CD strain following acute presentation; analgesia was evaluated using time for tail-withdrawal from hot water (55 degrees C). Both strains exhibited an analgesic response when latency to tail withdrawal was evaluated just prior to daily FSIA presentations over 15 total sessions indicating that these rat strains were behaviorally conditioned to this repeated stressor. However, the levels of conditioned analgesic responses to foot-shock were: greater in the CDF and most evident when rats were restrained on the shock-grid while being administered the foot-shock. All rats were quickly sacrificed following the 15th conditioning session to determine the effects of this stressor on neurotransmitter and neuroendocrine function in both strains of rat. Experimental subjects were exposed to the shock grid but not shocked during this last session. The following was found: plasma corticosterone (CORT) and prolactin levels and adrenal CORT levels were significantly increased by repeated stress in the CDF strain; only plasma CORT levels were elevated in the CD rat; pituitary immunoreactive beta-endorphin levels were significantly higher (+46%) amongst all experimental groups in the CDF strain, but stress was not observed to alter peptide steady-state levels in either strain; dopamine (DA), 5-hydroxytryptamine and metabolites (5-hydroxyindoleacetic acid and dihydroxyphenylacetic acid) levels were generally higher in the hypothalamus and frontal cortex of the CDF rat but turnover rates (implied from metabolite/amine ratios) indicated that these systems were more sluggish in this rat strain; hypothalamic DA turnover was significantly attenuated by repeated FSIA + restraint in both strains, but the dynamics of this effect appeared to be different between rat strains; and frontal cortex 5-HT turnover was significantly elevated by repeated FSIA + restraint in only the CDF rat. This research indicates that the CDF rat is extremely sensitive to an acute FSIA stress and it is less able than the CD rat to adapt to repeated presentation of this stress.
An injection of gamma-aminobutyric acid (GABA) and the GABA agonist, muscimol, into the dorsal raphe reduced both heart rate and blood pressure in the urethane-anesthetized rat. Picrotoxinin (3.4 nmol) did not affect blood pressure and slightly reduced the heart rate when injected into the dorsal raphe, but it blocked the decrease in both cardiovascular responses produced by GABA. These decreases in heart rate and blood pressure most likely result from stimulation of a GABAA receptor, as the GABAB agonist, baclofen, appeared to elevate heart rate and blood pressure by a mechanism occurring outside the dorsal raphe area. The changes in blood pressure and heart rate induced by muscimol occurred whether or not respiration was supported. Finally, it can be inferred that these GABAergic actions on blood pressure and heart rate probably involve both an inhibition of central sympathetic outflow and an excitation of parasympathetic outflow, as the quaternary muscarinic blocker, atropine methyl nitrate, blocked the decrease in heart rate induced by muscimol, but not the decrease in blood pressure.
The effect of direct intrastriatal injection of three organophosphate cholinesterase inhibitors, DFP (diisopropylphosphorofluoridate), soman (pinacolyl methylphosphonofluoridate) and sarin (isopropyl methylphosphonofluoridate) has been studied on locomotor activity in the rat. The degree of ChE inhibition has been monitored in the striatum, as well as in surrounding brain areas and blood, in order to verify the selectivity of the treatment and rule out effects attributable to actions in these areas and/or the periphery. It has been determined that while enzyme activity is inhibited in the striatum by all three compounds, only DFP significantly reduces locomotor activity at doses that produce no other observable behavioral deficits, or significant leakage into the periphery. Behavioral recovery occurs before enzyme activity returns to control levels. Possible contributions of DFP's action on other neurotransmitters and on ChE in other brain areas to the inhibition of locomotor activity are discussed.
Diisopropylfluorophosphate (81.5 nmol) was injected directly into the striata of rats to study changes in striatal metabolism of acetylcholine (ACh), 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) at early time points following acute irreversible inhibition of cholinesterase. Twenty minutes following the intrastriatal injection of diisopropylfluorophosphate, levels of striatal acetylcholine were elevated by 50%, but a decrease in KACh compensated for this change. At 1 h, levels of ACh were still elevated, but not significantly different from control values. However, KACh and, hence, ACh turnover were greatly enhanced at this time. Finally, at 24 h, striatal ACh content was only slightly elevated and KACh and the turnover rate of ACh had returned to control values. Striatal cholinesterase activity remained significantly inhibited at all three times. At none of these times was ACh content or turnover affected in the parietal cortex, hippocampus, hypothalamus, or medulla/pons. Neither dopamine and its metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid nor serotonin and its metabolite 5-hydroxyindoleacetic acid were significantly affected at any of the three times by intrastriatal diisopropylfluorophosphate treatment. Possible mechanisms of the changes in cholinergic parameters are discussed.
A health education campaign was carried out at the start of a large trial of screening for breast cancer in Edinburgh. After preliminary studies the campaign concentrated on talks to small groups of women by specially trained health visitors. Over a year, 12,000 women attended. Systematic evaluation after 12 months showed that selected women who heard the talks were more knowledgeable about breast cancer, and a random sample of women in Edinburgh had a small but significant improvement in knowledge compared with women in Aberdeen. However, the random sample did not report an increase in the practice of breast self-examination (BSE) and there was no increase in workload for general practitioners. It is suggested that BSE is more likely to be accepted if combined with a physical examination.
A women's health shop in Edinburgh was open for 16 months to provide information and advice in a non-clinical setting and to allow an interchange between informal and formal care in the community. Staffed by nurses, it was visited by 5664 women and 400 men, an average of 24 people each working day. The most popular topics for discussion were women's health problems, and 17% of women had a personal discussion with the nurse. The shop provided a useful and popular service and offered a practical method of furthering the concept of health promotion.
The role of serotonergic neurons in the dorsal raphe and median raphe in the pressor response to electrical stimulation of these areas, and the contribution of these neurons to the pressor response to serotonin (5-HT) in the anterior hypothalamus-preoptic area (AH/PO) have been studied by the use of local injections of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin selective for 5-hydroxytryptamine (5-HT). When blood pressure was recorded in urethane-anesthetized rats, selective lesions of 5-HT-containing neurons in the dorsal raphe nucleus reduced by 60% the pressor response to electrical stimulation (50 Hz, 100-150 microA, 0.3 msec pulse duration) of this nucleus. On the other hand, selective lesion of 5-HT-containing neurons in the median raphe nucleus had no effect on the pressor response to electrical stimulation of this area. Injection of 5,7-dihydroxytryptamine into the anterior hypothalamus/preoptic area resulted in an increased pressor response to the injection of 5-HT (5 nmol) into the lesioned area 10 days later. Furthermore, the destruction of 5-HT-containing neurons in the dorsal raphe nucleus resulted in an enhanced pressor response to the injection of 5-HT (5 nmol) into the anterior hypothalamus/preoptic area, while the destruction of 5-HT-containing neurons in the median raphe nucleus had no effect on the pressor response to the injection of 5-HT (5 nmol) into the anterior hypothalamus/preoptic area. Therefore, it appears that 5-HT neurons in the dorsal raphe nucleus are important in the pressor response to electrical stimulation and are involved in a pressor mechanism in the anterior hypothalamus/preoptic area.(ABSTRACT TRUNCATED AT 250 WORDS)