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G A Cottrell

Publications and source records attributed to G A Cottrell.

At least 55 records · Page 3Linked to original sources
PubMed1990

Effects of intrastriatal hormones on the dorsal immobility response in male rats.

Previous research has shown that estradiol administered either peripherally or directly into the striatum potentiates the dorsal immobility response (DIR) in ovariectomized female rats. Male rats are even more responsive than females to intrastriatal estradiol, and furthermore respond to the effects of catecholestrogens while females do not. In order to determine whether the heightened effects of estrogens in males are due to conversion to catecholestrogens, castrated male rats were given bilateral intrastriatal implants of moxestrol, which cannot be readily converted to a catecholestrogen, and diethylstilbestrol, which can. To determine whether the effects of intrastriatal estradiol in male rats might be related to the effects of androgens on the striatum, castrated male rats were given bilateral intrastriatal implants of testosterone, which can be aromatized to estrogen, and 5 alpha-dihydrotestosterone, which cannot. The effects of each of the hormones tested were measured against those of cholesterol (an inactive control substance) and 17 beta-estradiol. In each case the DIR was measured four hours after the hormone implant. Both synthetic estrogens and 17 beta-estradiol significantly potentiated the DIR, while neither of the androgens had an effect. Thus, the effects of estradiol, synthetic estrogens and catecholestrogens on the male striatum appear to be due to the estrogenic properties of these hormones.

Animals↗
PubMed1990

Actions of steroids and bemegride on the GABAA receptor of mouse spinal neurones in culture.

The effects of a synthetic and an endogenous steroid were studied on the GABAA receptors of isolated mouse spinal neurones, maintained in culture. Low doses of alphaxalone reversibly increased GABA-evoked whole-cell currents. Alphaxalone at higher doses (10-50 microM), when pressure ejected onto spinal neurones, also directly evoked a membrane chloride current. Such currents were reversibly suppressed by bicuculline (a GABAA antagonist) and enhanced by phenobarbitone. 5 beta-Pregnan-3 alpha-ol-20-one, a progesterone metabolite, dose-dependently potentiated the amplitude of GABA-evoked whole-cell currents. The mechanism of potentiation was examined at the single-channel level using outside-out patches from spinal neurones. The main action of the steroid on the GABAA receptor appears to be similar to that found for barbiturates, in that they prolonged GABA-activated bursts of channel openings. Bemegride had an antagonistic action on the GABAA receptor, suppressing both GABA- and pentobarbitone-evoked whole-cell currents to similar extents.

Animals↗
PubMed1989

Effects of intrastriatal hormones on the dorsal immobility response in the rat.

Previous research has shown that the dorsal immobility response (DIR) changes significantly in duration across the estrous cycle. In order to test whether gonadal steroid hormones act directly on the striatum to modulate this behavior, ovariectomized female Long-Evans hooded rats were given bilateral intrastriatal implants of 17 beta-estradiol, 2-hydroxyestradiol, progesterone, or cholesterol. These implants were made at one-week intervals, each animal receiving each treatment in a Latin square design. Four hours after each hormone implant, the animals were tested for the DIR. Only rats receiving the intrastriatal 17 beta-estradiol implant were significantly different from those receiving cholesterol, and showed greatly potentiated DIR's.

Animals↗
PubMed1989

An electrophysiological investigation of the characteristics and function of GABAA receptors on bovine adrenomedullary chromaffin cells.

The characteristics and function of gamma-aminobutyric acidA (GABAA) receptors expressed on bovine chromaffin cells in culture have been investigated using patch-clamp techniques. In voltage-clamped whole-cells, locally applied GABA (100 microM) evoked a transmembrane chloride current which demonstrated outward rectification. The amplitude of such currents was reversibly suppressed by the GABAA receptor antagonists bicuculline, picrotoxin and RU5135, and enhanced by the general anaesthetic propanidid. Glycine (100 microM) and baclofen (100 microM) were ineffective as agonists. In support of a physiological role for GABA in the adrenal medulla, the co-existence of GABAA and nicotinic acetylcholine (ACh) receptors was demonstrated on whole cells and outside-out membrane patches. Ionophoretically applied GABA reduced the amplitude of depolarization and action potential discharge occurring in response to locally applied ACh (100 microM), but had no effect upon the underlying ACh-induced current. In addition, an excitatory action of GABA was demonstrated by recording action potential waveforms in cell-attached patches. The results are discussed in the context of a GABA-ergic regulation of catecholamine secretion.

Acetylcholine↗
PubMed1989

Effects of intracerebral estradiol on the dorsal immobility response in the rat.

The effects of intracerebral implants of 17 beta estradiol and cholesterol in five brain regions were tested on the duration of the dorsal immobility response in ovariectomized female rats. The dorsal immobility response was significantly prolonged by 4-hr implants of 17 beta estradiol in the dorsal striatum and nucleus accumbens, but not in the cortex, the globus pallidus, or the substantia nigra pars compacta. These data further support previous evidence that estradiol acts directly on the striatum to affect behavior in the rat.

Animals↗
PubMed1989

The effects of intrastriatal hormones on the dorsal immobility response in gonadectomized male and female rats.

Previous research has shown that intrastriatal estradiol potentiates the dorsal immobility response in ovariectomized female rats. In order to test whether the gonadal steroid hormones act on the male striatum in the same way, gonadectomized male and female Long-Evans hooded rats were given bilateral intrastriatal implants of 17 beta-estradiol (17 beta-E2), 17-alpha-estradiol (17-alpha-E2), 2-hydroxyestradiol (2-OH-E2), 4-hydroxyestradiol (4-OH-E2), or cholesterol. Four hours after the hormone implant the dorsal immobility response (DIR) was measured. In the ovariectomized females, the DIR was significantly potentiated only by 17 beta-E2 and 17-alpha-E2. In the castrated males, the DIR was significantly potentiated by 17 beta-E2, 17-alpha-E2, 2-OH-E2, and 4-OH-E2. While the DIR durations did not differ between males and females after intrastriatal cholesterol, the males had significantly longer DIR durations after each of the other hormones. These results are discussed in terms of estradiol stereospecificity and the properties of catechol estrogens in male and female rats.

Animals↗
PubMed1988

Hippocampal kindling-induced after-discharge and behavioural depression: immediate and long-term attenuation by opiate antagonists.

Hippocampal kindling results in tonic-clonic convulsions followed by a pronounced period of behavioural depression. The effect of the opiate antagonists, naltrexone and naloxone, on the duration of the after-discharge and behavioural depression was investigated. Naltrexone, injected s.c. 60 min before, significantly reduced the behavioural depression at doses as low as 0.6 mg/kg, but had no effect on the after-discharge even at higher doses. One day later, the behavioural depression was still reduced in some animals and the after-discharge was significantly decreased following the higher doses (0.24-0.48 mg/kg). Naloxone, injected s.c., 10 min before, significantly reduced the behavioural depression at a dose as low as 0.002 mg/kg and also reduced the duration of the after-discharge at some doses. Naloxone did not exert any significant effects 24 h later. Naltrexone, injected i.c. 60 min before kindling in a dose of 1 microgram, significantly attenuated the behavioural depression and had no effect on the after-discharge. The behavioural depression was still attenuated 24 and 48 h later. The involvement of mu-receptor-related endogenous opioid mechanisms in postictal brain processes is suggested. The long-term effects might be related to receptor 'activation' during the immediate period due to an interaction between the antagonist and the kindling experience.

Animals↗
PubMed1988

Actions of baclofen on components of the Ca-current in rat and mouse DRG neurones in culture.

1. Ca currents in rat and mouse sensory dorsal root ganglion (DRG) neurones were inhibited by concentrations of (-)-baclofen as low as 1 micron. The proportion of neurones responding to baclofen was low (less than 20%), except in young cultures of neonate rat DRG neurones (3 days in culture), where 86% of the neurones were responsive. 2. Three types of unitary Ca currents were observed in the rat DRG neurones, corresponding to the T-, N- and L-type currents of chick DRG neurones. 3. Baclofen produced two types of response on whole-cell currents of DRG neurones from both species. The first was on an early inactivating component of the Ca current. This early current was partially inactivated at a holding potential of -40 mV. It was also reduced during the second of a pair of depolarizing command pulses. The results suggest that this action of baclofen is due to an action on an N-type component of the current. The second response to baclofen persisted throughout the command step and was not reduced during the second of a pair of command pulses, indicating that this effect is due to an action on the L-type current. 4. Unitary or ensemble Ca currents recorded in cell-attached patches, on neurones previously shown to respond to baclofen in whole-cell clamp mode, were generally not inhibited by baclofen application external to the patch electrode. This indicates that a readily diffusible internal second messenger substance is probably not involved in coupling the GABAB receptor to the ion channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Immediate and long-term effects of opiate antagonists on postictal behaviour following amygdala kindling in the rat.

Male Wistar rats implanted with bipolar electrodes in the amygdaloid complex were kindled. Subcutaneous injection of naloxone or naltrexone in low doses--0.12 and 0.24 mg/kg, respectively--dramatically reduced the postictal behavioural depression (BD) at 10 or 60 min. Remarkably, the BD was still reduced one day later. It would appear that the brain mechanisms involved in postictal BD use mu-receptors since BD is quite sensitive to low doses of the preferential antagonists naloxone and naltrexone. The long-term effects, the most novel aspect of these studies, are probably related to immediate effects but could be produced through slow genomic processes or alteration of the response to endogenously released enkephalins.

Amygdala↗
PubMed1987

Modulation of the GABAA receptor by progesterone metabolites.

The naturally occurring progesterone metabolites 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione reversibly enhance membrane currents elicited by locally applied GABA in bovine adrenomedullary chromaffin cells. Such potentiation was not influenced by the benzodiazepine antagonist Ro 15-1788. At concentrations in excess of those necessary to evoke potentiation of GABA currents, 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregane-3,20-dione directly activated a membrane conductance. The resulting currents were potentiated by phenobarbitone and diazepam, and abolished by the GABAA-receptor antagonist, bicuculline. On outside-out membrane patches, 5 beta-pregnan-3 alpha-ol-20-one and 5 beta-pregnane-3,20-dione activated single channel currents of similar amplitude to those evoked by GABA. The results suggest that certain naturally occurring steroids potentiate the actions of GABA and, additionally, directly activate the GABAA receptor.

Adrenal Medulla↗
PubMed1987

Prevention of cysteamine-induced myoclonus blocks the long-term inhibition of kindled seizures.

In kindled rats, the administration of cysteamine (CSH, 200 mg/kg, i.p.) 4 h prior to a kindled seizure leads to long-term (up to 10 days) inhibition of kindled seizures. CSH (200 mg/kg, i.p.) also induces myoclonic seizures in kindled rats. We suggest that the long-term inhibition of kindled seizures might be the result of the myoclonus, not the somatostatin depletion as previously suggested. Prior administration of the short-acting benzodiazepine midazolam (5 mg/kg, i.p.) eliminated the CSH-induced myoclonus and prevented the long-term inhibition of kindled seizures. These results suggest that the CSH-induced long-term inhibition of kindled seizures is the result of an interaction between the myoclonic seizure and a subsequent kindled seizure.

Animals↗
PubMed1987

Suppression of kindled seizures by cysteamine: dependence on injection-to-kindled seizure interval.

A single injection of cysteamine, 200 mg/kg i.p., administered 4 h before a kindling session induces long-term suppression of kindled seizures. Injection of cysteamine 2, 4 or 6 h after or 24 h before the kindling session is either less effective or ineffective. The present series of experiments shows that the injection-to-kindled seizure interval is critically important for the long-term inhibition. We propose that the anticonvulsant effect is caused by an interaction of the cysteamine and the kindled seizure.

Amygdala↗
PubMed1987

Baclofen exacerbates epileptic myoclonus in kindled rats.

Electrically kindled rats exhibit myoclonic jerks (1-25/min for 30-90 min) when injected with 200 mg/kg i.p. cysteamine. L-Baclofen, 10 mg/kg i.p. injected 45 min prior was not anticonvulsant but rather exacerbated the myoclonus. Furthermore, baclofen itself induced myoclonus in 29% of kindled rats at 10 mg/kg and in 100% of kindled rats at 15 mg/kg. These findings suggest that caution should be exercised before proposing the use of baclofen as an anticonvulsant or indeed using baclofen in patients who are predisposed to seizures.

Animals↗
PubMed1987

Modulation of GABAA receptor activity by alphaxalone.

The modulation of the gamma-aminobutyric acidA (GABAA) receptor by alphaxalone has been investigated by use of voltage-clamp recordings from enzymatically isolated bovine chromaffin cells maintained in cell culture. Alphaxalone (greater than 30 nM) reversibly and dose-dependently potentiated the amplitude of membrane currents elicited by locally applied GABA (100 microM). The potentiation was not associated with a change in the reversal potential of GABA-evoked currents and was not influenced by the benzodiazepine receptor antagonist, Ro15-1788 (300 nM). At relatively high concentrations (greater than 1 microM), alphaxalone directly elicited a membrane current. It is concluded that such currents result from GABAA receptor activation since they were reversibly suppressed by bicuculline (3 microM), dose-dependently enhanced by phenobarbitone (100-500 microM), and had a similar reversal potential (approximately 0 mV) to currents elicited by GABA. Additionally, on outside-out membrane patches, alphaxalone activated single channel currents with amplitudes and a reversal potential similar to those evoked by GABA. Alphaxalone (30 nM-1 microM) had no effect upon the amplitude of membrane currents elicited by locally applied acetylcholine (ACh) (100 microM). However, higher concentrations of alphaxalone (10-100 microM) reversibly suppressed ACh-evoked currents, the IC50 for blockade being 20 microM. The beta-hydroxy isomer of alphaxalone, betaxalone (100 nM-1 microM), did not potentiate GABA-induced currents, nor did higher concentrations of the steroid (10-100 microM) directly evoke a membrane current. However, over the latter concentration range, betaxalone suppressed the amplitude of currents elicited either by GABA or ACh. The relevance of the present results to the anaesthetic action of alphaxalone is discussed together with the broader implications of steroidal modulation of the GABAA receptor.

Acetylcholine↗