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Biomedical subjects

D M Jackson

Publications and source records attributed to D M Jackson.

At least 127 records · Page 7Linked to original sources
PubMed1985

Bromocriptine potentiates the behavioural effects of directly and indirectly acting dopamine receptor agonists in mice.

After an initial period of depression which lasted up to 90 min following injection, bromocriptine (BRC, 5-20 mg/kg, IP) produced dose-dependent and long lasting (7 h) locomotor stimulation in mice. The locomotor stimulation was antagonised by reserpine, alpha-methyl-p-tyrosine (AMPT) or haloperidol. The blockade by AMPT of BRC's locomotor stimulant effect was reversed by prior treatment of the mice with a low, behaviourally inactive dose of L-Dopa plus benserazide. In mice pretreated with reserpine, BRC enhanced the stimulant action of d-amphetamine. Moreover, in mice pretreated with reserpine plus AMPT, BRC significantly enhanced the locomotor stimulant effect of apomorphine. This ability of BRC to enhance the effect of apomorphine commenced as soon as 20 min after BRC administration and lasted for at least 8 h. The dopamine (DA) uptake inhibitor and DA receptor agonist nomifensine potentiated and prolonged the stimulant effect of BRC while inhibitors of the neuronal uptake of noradrenaline (desipramine) and 5-hydroxytryptamine (fluoxetine) were without marked effect. The results clearly show that BRC, in behavioural terms, has no efficacy per se at the postsynaptic DA receptor and that it requires either DA or the administration of an exogenous agonist such as apomorphine for the expression of its effects.

Animals↗
PubMed1985

Hypothesis: bromocriptine lacks intrinsic dopamine receptor stimulating properties.

Bromocriptine (BRC) produced neither locomotor stimulation nor stereotyped behavior in mice and rats pretreated with reserpine plus alpha-methyl-p-tyrosine (AMPT). However, the blockade of locomotor stimulation in mice by AMPT could be reversed by their prior treatment with a low, behaviorally inactive dose of L-DOPA. BRC potentiated the stereotypy (rats) and locomotor stimulation (mice) produced by apomorphine in animals pretreated with reserpine plus AMPT. Moreover, BRC potentiated the stimulant effect of d-amphetamine in reserpinized mice, while nomifensine, but not fluoxetine or desipramine, potentiated the stimulant effect of BRC in mice. After direct application to the nucleus accumbens or caudate nucleus of rats, BRC was inactive. However, when BRC and DA were applied together to the nucleus accumbens, BRC enhanced the stimulant effect of DA. These data show that BRC by itself does not cause behavioral stimulation in rodents. Despite having affinity for the DAD 2-receptor, BRC is incapable of causing excitation in rats and mice unless another DA-receptor agonist such as apomorphine or DA is present. The data are discussed in relation to the published literature and the hypothesis presented that BRC affects the signal transmitted by DA-receptor agonists such as apomorphine at or beyond the postsynaptic DA-receptor.

Adenylyl Cyclases↗
PubMed1985

The effect of dopamine receptor agonist treatment on haloperidol-induced supersensitivity in mice.

Mice were pretreated with haloperidol (HP) (3-4 mg/kg/day in drinking water) or vehicle for 21 days. On the 25th day, HP-pretreated mice were supersensitive to the locomotor stimulant effects of apomorphine (after acute premedication with reserpine and alpha-methyl-p-tyrosine). This behavioural supersensitivity was accompanied by a 25-39% increase in the number of [3H]-spiperone binding sites in the striata of HP-pretreated mice. Short-term repeated administration of the dopamine (DA) agonist drugs d-amphetamine and L-DOPA during the HP withdrawal phase (days 22, 23 and 24) had no effect on either measure of DA receptor supersensitivity. In contrast, the administration of apomorphine on days 22, 23 and 24 enhanced the HP-induced behavioural supersensitivity but decreased the HP-induced elevation of the number of [3H]-spiperone binding sites. Apomorphine treatment alone did not alter either measure. The results do not support the hypothesis that supersensitive DA receptors can be down-regulated by short-term treatment with DA agonist drugs and, moreover, indicate that important discrepancies may exist between behavioural and biochemical measures of DA receptor supersensitivity.

Animals↗
PubMed1985

The quasi-morphine withdrawal syndrome: effect of cannabinol, cannabidiol and tetrahydrocannabinol.

Delta-9-tetrahydrocannabinol (THC), the main psychoactive principle of cannabis, has been shown to attenuate the exhibition of signs of the quasi-morphine withdrawal syndrome in rats. Cannabinol (CBN) showed the same activity but required a dosage of approximately eight times that of THC to produce an equivalent effect. Cannabidiol was without effect at the dosage levels used. The efficacy of these cannabinoids and the potency differences recorded in this study are in accord with their effects on other behaviours, both in experimental animals and in man. The activity of THC and CBN was not affected by the narcotic antagonist, naloxone.

Animals↗
PubMed1985

The effect of atracurium or fazadinium on intra-ocular pressure. A comparative study during induction of general anaesthesia.

The effect of atracurium 0.6 mg/kg (group A; n = 11) and fazadinium 1 mg/kg (group F; n = 11) on intraocular pressure (IOP) was investigated in 22 patients during induction of anaesthesia with thiopentone 4 mg/kg and fentanyl 0.015 mg/kg. IOP was significantly reduced (p less than 0.01) in all patients following induction of anaesthesia. Intubation produced a rise in IOP in all patients but this was not statistically significant and remained below pre-induction values. The changes were similar in each group. Both of these neuromuscular blockers appear suitable relaxants to use for intraocular surgery.

Adult↗
PubMed1985

The effect of nedocromil sodium and sodium cromoglycate on antigen-induced bronchoconstriction in the Ascaris-sensitive monkey.

Nedocromil sodium inhibited the bronchoconstriction caused by antigen challenge in Ascaris-sensitive monkeys and in addition it prevented the release of histamine from mast cells lavaged from sensitive monkeys. Sodium cromoglycate was relatively inactive in both these systems. It is suggested that nedocromil sodium can stabilize both mucosal and connective tissue mast cells and may represent a new type of drug.

Animals↗
PubMed1984

Passive avoidance in rats: disruption by dopamine applied to the nucleus accumbens.

The acquisition of a one-trial step-through passive avoidance task was examined in rats following the administration of nialamide IP and dopamine (DA) or saline into the nucleus accumbens. DA-treated rats displayed impaired learning of the task as evidenced by their lower step-through latencies on a retest trial 7 days later. The specificity of this impairment was studied in a 2 x 2 design involving intracerebral injections prior to both training and testing trials. It was found that DA treatment prior to the training trial disrupted learning or memorization of the task but that DA did not affect performance or retrieval and did not induce state-dependent learning. These findings suggest that DA applied to the nucleus accumbens does not facilitate learning per se.

Animals↗
PubMed1984

Dopamine applied into the nucleus accumbens and discriminative avoidance in rats.

The actions of dopamine (DA) administered into the nucleus accumbens on motor function and discrimination were examined in rats trained to perform a discriminative conditioned avoidance response (DCAR). alpha-Methyl-p-tyrosine was found to suppress performance of the CAR although it did not impair discrimination. The administration of DA reinstated CAR performance but it also increased discriminative errors. Multivariate comparisons suggested that both of these effects were closely related to the stimulation of intertrial crossings by DA.

Animals↗
PubMed1983

Involvement of catecholamines in acute tolerance to ethanol in mice.

The percentage of mice able to remain on a rolling drum for 45 s was recorded at 1.25 min and 30 min after administration of ethanol (2.4 g/kg). Though there was no significant difference in brain ethanol levels at the two test times, performance was markedly different with significantly fewer mice able to remain on the drum at 1.25 min than at 30 min. This phenomenon, known as acute tolerance, was antagonised by pretreating mice with haloperidol (0.4 mg/kg), FLA-63 (25 mg/kg), diethyldithiocarbamate (400 mg/kg), phenoxybenzamine (40 mg/kg), phentolamine (20 mg/kg), yohimbine (3 mg/kg) and clozapine (1 mg/kg), but not by spiperone (0.16 mg/kg), alpha-methyl-p-tyrosine (300 mg/kg) or phenobarbitone (10 mg/kg). The relative potencies of the effective blocking agents suggest that alpha 2-receptors may play an important role in mediating acute ethanol tolerance.

Animals↗
PubMed1983

Chronic L-dopa treatment of rats and mice does not change the sensitivity of post-synaptic dopamine receptors.

The effects of L-Dopa + benserazide (L-Dopa + B) treatment on pre- and postsynaptic dopamine (DA) receptors were studied. Mice treated once daily P.O. with L-Dopa (200 mg/kg) + B (50 mg/kg) or vehicle for 10 days were used on the 11th day. After premedication with reserpine and alpha-methyltyrosine (alpha-MT), apomorphine (0.5-2.0 mg/kg) produced locomotor stimulation which was of equal intensity in the 3 treatment groups, even when the treatment dose of L-Dopa was increased to 400 mg/kg per day. In contrast, low doses of apomorphine (0.1-0.5 mg/kg) produced locomotor depression in B- and vehicle-treated mice but not in L-Dopa + B-treated mice. In rats treated I.P. twice daily with L-Dopa (200 mg/kg) + B (50 mg/kg), B (50 mg/kg) or vehicle for 12 days, apomorphine produced an equivalent degree of stereotypy on the 13th day in each of the 3 treatment groups. There were no treatment group differences in the binding of [3H]-spiperone or [3H]-leu-enkephalin to rat striatal membranes. The data suggest that long-term L-Dopa + B treatment of mice and rats does not change the sensitivity of postsynaptic DA receptors but may affect the sensitivity of DA autoreceptors.

Animals↗
PubMed1983

Chronic haloperidol and adrenergic receptor sensitivity in the rat.

Rats were administered haloperidol (3-4 mg/kg/day) in their drinking water for 42 days, and experiments conducted on the seventh day of withdrawal. Anaesthetized haloperidol treated rats exhibited a similar mean blood pressure (BP) and heart rate (HR) response to control rats when challenged with phenylephrine (IV). When similarly pretreated rats were challenged with one of four possible doses of clonidine (IV), haloperidol treated rats were less sensitive than control rats to clonidine's hypertensive action, but there were no effects of treatment on the hypotensive (BP) effect of clonidine nor on its bradycardic effect. When one of six possible doses of tyramine was administered a similar mean BP response was seen in both treatment groups, but the positive HR response in the haloperidol-treated group was much less than in the vehicle-treated group. Atria isolated from haloperidol treated or control rats revealed a similar chronotropic response to noradrenaline and tyramine challenge. These data indicate that chronic haloperidol does not cause a generalized change in alpha-adrenergic receptor sensitivity. Nevertheless, it is clear that haloperidol has produced changes in the cardiovascular response of rats to these drugs.

Animals↗
PubMed1983

Self-stimulation of the nucleus accumbens and some comparisons with hypothalamic self-stimulation.

Rats were trained to respond for electrical stimulation of the nucleus accumbens (ACB) or lateral hypothalamus (HYP) in a shuttle-box apparatus. Whereas the HYP rats showed rapid acquisition and stabilization of performance, the ACB rats were slow to learn the task and commonly took longer than 20 daily sessions to stabilize. Once stabilized, both groups responded with similarly vigorous performance. All rats displayed a predominantly locomotor behaviour, which was almost totally devoid of exploratory behaviours typically associated with self-stimulation. The absence of stimulus-bound behaviours was particularly notable in the ACB group. These rats, but not the HYP rats, showed an increase in the latency to initiate stimulation during the daily 25-min test sessions. Depriving the animals of a single self-stimulation session caused a decrease in the latency of ACB rats to initiate on the following day while having no effect on the HYP rats. All ACB rats gradually developed convulsive seizures during the first 3 weeks of testing which subsequently became more frequent and severe. None of the HYP rats showed any involuntary motor effects. The results show that ACB self-stimulation is a very different phenomenon to HYP self-stimulation, and suggest that, in addition to reward and aversion, ACB self-stimulation may involve a stereotyped ritual controlled partly by adaptation and conditioning.

Animals↗
PubMed1983

Changes in the bronchial reactivity of dogs caused by exposure to sulphur dioxide.

The effects of a 2 h exposure to 250 and 400 p.p.m. of SO2 delivered via an endotracheal tube on the reactivity of the dog lung have been studied. Forty-eight hours after exposure to 250 p.p.m. SO2 base-line values of total lung resistance and dynamic lung compliance were unchanged but there was an increase in the bronchoconstrictor response to histamine (20 micrograms/kg I.V.). This enhanced response was vagally dependent. The response of lung irritant receptors to histamine (20 micrograms/kg I.V.) was also increased in these animals. Forty-eight hours after exposure to 400 p.p.m. SO2 resting total lung resistance had increased and resting dynamic lung compliance had fallen. Vagotomy produced a small but insignificant fall in resting total lung resistance. Changes in total lung resistance produced by acetylcholine (40 micrograms/kg I.V.) histamine (20 micrograms/kg I.V.) and 5-hydroxytryptamine (20 micrograms/kg I.V.) were all increased after exposure and these increases were significantly reduced by vagotomy. The falls in dynamic lung compliance produced by these agents were not enhanced by exposure to SO2. The rise in total lung resistance by bilateral vagal stimulation was increased 48 h after exposure to 400 p.p.m. SO2. Exposing dogs to SO2 produced an increase in the reactivity of the lung principally by the enhancement of reflexes. The mechanisms involved are discussed.

Acetylcholine↗
PubMed1983

Laboratory infection of primates with Ascaris suum to provide a model of allergic bronchoconstriction.

Wild-caught non-human primates are naturally sensitive to Ascaris antigen and provide a useful model for studying atopic asthma. The present study was carried out to determine the effect of experimentally infecting home-bred macaques with the nematode Ascaris suum and hence provide an alternative for the naturally occurring model. Following oral infection with the parasite the animals developed a blood eosinophilia and specific antibodies to purified Ascaris antigen. These antibodies appeared to be of the IgE class as they could be detected by a radiometric assay using a radiolabelled antibody to human IgE. However, on further investigation, using the passive cutaneous anaphylaxis test, two classes of antibody were found, a heat labile (56 degrees C) and a heat stable antibody. Lung lavage cells taken from monkeys infected with Ascaris suum were shown to include cells morphologically characteristic of mast cells and released histamine when challenged in vitro with Ascaris antigen. Hence this model of immediate hypersensitivity provides a simple alternative to the less accessible natural model.

Animals↗
PubMed1983

Ascaris-induced bronchoconstriction in primates experimentally infected with Ascaris suum ova.

Bronchial provocation with Ascaris allergen evoked bronchoconstriction in home-bred Macaca arctoides monkeys sensitized by experimental infection with embryonated Ascaris suum ova. Inhalation of Ascaris allergen by aerosol prior to infection produced no changes in lung function. In infected animals total lung resistance (RL) increased and dynamic lung compliance (Cdyn) decreased following Ascaris inhalation. The changes in lung function reached a peak, 2-5 min after allergen inhalation, lasted for approximately 30 min and were associated with increases in arterial plasma histamine levels and decreases in arterial Po2 levels. Reproducible changes in lung function were obtained when the monkeys were challenged at bi-weekly intervals and lung sensitivity to Ascaris was maintained for at least 6 months. Histamine produced similar changes in RL and Cdyn before and after infection. Ascaris-induced bronchoconstriction was reversed by the beta 2-stimulant, salbutamol, and was partially reversed by cholinergic blockade with atropine. The responses were not inhibited by antihistamines or sodium cromoglycate although a new anti-allergic agent, FPL 58668 (disodium salt), inhibited Ascaris-induced bronchoconstriction and the increase in plasma histamine levels seen after Ascaris inhalation. Ascaris-induced bronchoconstriction in experimentally infected monkeys provides an animal model demonstrating many of the characteristics of allergic asthma in man and does not require the use of wild-caught monkeys.

Airway Resistance↗
PubMed1982

Chronic L-DOPA-pretreatment of rats: an electrophysiological and biochemical study in the basal ganglia.

Treatment of rats with L-DOPA (251.25 mg as the methyl ester HCl/kg) plus benserazide (B, 50 mg/kg) (L-DOPA+B), twice daily (i.p.) for 5 days or 12 days resulted in the dopamine (DA) neurons of the substantia nigra pars compacta becoming subsensitive to the rate-depressing effects of D-amphetamine (i.v.) 16 to 24 h after the last chronic drug dose. In contrast, pretreated rats were significantly less sensitive than control rats to the rate depressant effects of apomorphine (i.v.) after 12, but not 5 days of L-DOPA+B-pretreatment. After 5, but not 12 days of L-DOPA+B-pretreatment, a significant increase in the number of spontaneously active DA neurons was noted in the substantia nigra pars compacta. Caudate tyrosine hydroxylase was examined and a significant increase in apparent Vmax was noted after 5 days of L-DOPA+B, with no apparent change being noted in Km for cofactor. At this time, no change was noted in caudate DA or HVA concentrations. Several distinct processes may be occurring in response to the L-DOPA+B-pretreatment: (1) the DA autoreceptors located on cell bodies in the substantia nigra have become subsensitive after 12 days of L-DOPA+B-pretreatment; (2) the subsensitivity to D-amphetamine seen after both chronic schedules is probably unrelated to the subsensitive DA autoreceptors and may depend upon homeostatic alterations in neurotransmitter systems other than those utilising DA; (3) the activation of tyrosine hydroxylase may be a reflection of the increase in the number of spontaneously active units.

3,4-Dihydroxyphenylacetic Acid↗