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J D Stephenson

Publications and source records attributed to J D Stephenson.

84 records · Page 5Linked to original sources

Actions of dexamphetamine and amphetamine-like amines in chickens with brain transections.

1. A method for preparing the encéphale isolé preparation in young fowls is described. Certain important differences were found between electrocortical activity of chicken and mammalian encéphale isolé preparations. Electrocortical effects of excitant sympathomimetic amines and their antagonism were readily quantified because of stable electrocortical activity of the chick encéphale isolé preparation.2. Amphetamine-like excitant amines ((+)- and (-)-amphetamine, alpha-methyltryptamine, tryptamine, beta-phenethylamine, cyclopentamine, beta-tetrahydronaphthylamine and tuaminoheptane) evoked electrocortical desynchronization in chick encéphale isolé preparations, confirming the central origin of these effects. Behavioural changes were also observed.3. The electrocortical response to these amines was antagonized by methysergide, a selective tryptamine antagonist and by a catecholamine, alpha-methylnoradrenaline. Behavioural changes were also antagonized.4. Electrocortical desynchronization to dexamphetamine was prevented by an anterior transection of the brain which separated the telencephalon from the diencephalon. More posterior transections reduced the duration of the electrocortical response to dexamphetamine; intensity of response was either increased or decreased.

Amines↗

Effects of catecholamines infused into the brain of young chickens.

1. (-)-Noradrenaline, (-)-alpha-methylnoradrenaline and (-)-isoprenaline were infused into various brain regions of 12-21 day chicks. When infused into the hypothalamic area, but not the cerebral hemisphere or posterior mesencephalon, these amines produced behavioural sleep, lowered temperature and blood pressure and reduced oxygen consumption; electrocortical sleep activity usually ensued but this was not marked and frequently dissociation between electrocortical activity and behaviour occurred. After monoamine oxidase inhibition, which prolonged the action of noradrenaline, dopamine had similar effects.2. The effects of the catecholamines were prevented or substantially reduced by pretreatment with phenoxybenzamine given intravenously or into the hypothalamus but not by intravenous injection of propranolol. However, intrahypothalamic infusion of propranolol prevented the temperature, but not the behavioural effects of noradrenaline. The implications of this are discussed.3. That the effects were similar but more intense, apart from electrocortical changes, and of longer duration than those seen after intravenous injection of catecholamines suggests that in young chicks these amines penetrate from the blood into the brain and elicit their effects through a localized region, presumably the hypothalamus.

Animals↗

Importance of forebrain cholinergic and GABAergic systems to the age-related deficits in water maze performance of rats.

The present study investigated the performance of rats at 3-4 months and 21 months of age in the Morris water maze and correlated age-related cognitive deficits with changes in both cholinergic and GABAergic systems in the frontal cortex. The older rats were divided into two groups, unimpaired old and impaired old according to their ability to find a hidden submerged platform in the water maze, for electrophysiological, neurochemical, and morphological studies. The firing rate of frontal cortical neurones was recorded from the motor area of the frontal cortex under urethane anaesthesia and was found to be significantly slower in the two aged groups of rats compared to the young rats, but there were no differences between the two aged groups. The sensitivity of frontal cortex neurones of the impaired and unimpaired old age groups to ACh and to carbachol was significantly lower than that of the young group, but there were no differences between the two old age groups. In contrast, sensitivity of frontal cortex neurones to bicuculline was significantly higher in the aged rats compared with the young rats and was significantly greater in the impaired old rats than in the unimpaired old rats. The sensitivity of cortical neurones to glutamate was unaffected by age. There were also significant correlations between the percentages of cortical neurones responding to ACh and bicuculline and different parameters of water maze acquisition during days 7-8, but not during days 2-3, when spatial learning had not begun, and days 13-14, when spatial learning was complete. Biochemical and morphological analyses did not show any significant differences in ChAT activity and AChE-positive fibre density in the frontoparietal cortices of the three groups of rats. The results demonstrate that the learning deficit observed in old age rats cannot be adequately explained solely by a reduction in cholinergic receptor sensitivity and that an age-related increase in GABAergic tone may be a more important determinant of cognitive impairment.

Acetylcholine↗

Effects of tetrahydro-9-aminoacridine on the electrocorticogram of rats with a unilateral lesion of the nucleus basalis magnocellularis.

The effects of tetrahydro-9-aminoacridine (THA) were studied on the electrocortical activity of control rats and of rats with a unilateral lesion of the nucleus basalis magnocellularis (NBM) produced by alpha-amino-3-hydroxy-4-isoxozole propionic acid (AMPA). This lesion almost completely deprived the lesioned hemisphere of its cholinergic innervation. In control rats, THA (10 mg/kg i.p.) increased the amplitude of the slow components of the electrocorticogram (less than 9 Hz). These effects were antagonised by atropine (5 mg/kg i.p.). Lesion of the NBM alone decreased the amplitude of frequencies in the 12-16 Hz frequency band but did not significantly affect the slower frequencies. THA (10 mg/kg) restored the amplitude of the 12-16 Hz activity to the level seen in control rats before THA but did not affect activity in the other frequency bands. The results suggest that THA requires some residual cholinergic innervation in order to exert its effect.

Animals↗

Theta driving both inhibits and potentiates the effects of nicotine on dentate gyrus responses.

The medial septal area of conscious rats was stimulated through previously implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta. Two weeks later in the anaesthetized rats the effects of a single subcutaneous injection of nicotine (0.4 mg x kg(-1)) on fEPSPs, evoked in the dentate gyrus by separate stimulation of the MPP and LPP, were studied and compared with those obtained in controls. Nicotine increased the firing of locus coeruleus neurones and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP stimulation. Prior theta driving considerably increased the effect of nicotine on the responses evoked by stimulation of the MPP and abolished the nicotine-induced potentiation of the responses evoked by stimulation of the LPP. The results are attributed to theta driving increasing the amount of noradrenaline released by nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting potentiation at the medial perforant path synapse and a long-lasting depression at the lateral perforant path synapse.

Animals↗

Biphasic effects of atropine on sensory-evoked hippocampal rhythmical slow activity in urethane-anaesthetized rats.

This study investigated the response of hippocampal RSA, recorded from electrodes in CA1 and the contralateral dentate gyrus of urethane-anaesthetized rats, to atropine sulphate administered at 15 min intervals in a cumulative dose-response schedule (1, 3, 10, 50 and 50 mg x kg(-1) i.p.). The power of CA1 and dentate gyrus RSA in the 3-7 Hz band was increased after administering the first 3 doses of atropine (1, 3 and 10 mg x kg(-1) cumulatively) in rats held in the stereotaxic frame or removed from the frame and given electrical sensory stimulation to the base of the tail. This increase in RSA was dependent on sensory input, since it was not seen in animals outside the frame unless sensory stimulation was given, and it was abolished by increasing the dose of atropine (an additional 50 and 50 mg x kg(-1) cumulatively). Methylatropine (6 mg x kg(-1) i.p.) did not increase RSA power. The biphasic effect of atropine on sensory-evoked hippocampal RSA activity may be explained by differential effects at pre- and post-synaptic sites e.g. in the septo-hippocampal system or on pathways processing sensory information.

Animals↗

Pharmacology of the central control of micturition.

Micturition is the process whereby urine is collected in the bladder until such time as it is convenient to void. The two phases of the cycle are controlled by several reflexes but the act of voiding is usually initiated voluntarily. To date, pharmacological research on the central control of micturition has concentrated on influences of the brain stem and spinal cord, and in particular of the locus coeruleus, the "pontine micturition reflex centre". Studies have shown that spontaneous bladder motility is affected by agents acting upon receptors for acetylcholine, noradrenaline, dopamine, opioids, GABA and glutamate. It is now necessary to extend these studies to conscious animals so that reflex activity is not affected by anaesthesia and the effects of drugs on the collecting and emptying phases can be examined.

Animals↗