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Biomedical subjects

B T Davies

Publications and source records attributed to B T Davies.

At least 19 recordsLinked to original sources

Effects on ingestive behavior in rats of the alpha 1-adrenoceptor agonist cirazoline.

Microinjections of various alpha 1-adrenoceptor agonists including phenylephrine and phenylpropanolamine into the paravenricular hypothalamic nucleus (PVN) suppress food intake in rats, suggesting that this receptor type might act in opposition to previously identified facilatory PVN alpha 2-adrenoceptors in the modulation of feeding. In the present experiments, we examine the effects on food and water intake of intra-PVN as well as systemic injection of cirazoline, a highly potent alpha 1-adrenoceptor agonist. In Experiment 1, intra-PVN microinjection of cirazoline (0, 3, 6, 12 and 24 nmol) suppressed food intake (ED50 = 23.4 nmol) without significant effects on water intake. In Experiment 2, systemic injection of cirazoline (0, 0.05, 0.1, 0.2, 0.4 mg/kg) also markedly suppressed food intake (ED50 = 0.05 mg/kg i.p.), with a less potent action on water intake (ED50 = 0.22 mg/kg i.p.). The results of this study as well as our previous investigations strongly support the notion that alpha 1-adrenoceptors within rat PVN act to reliably suppress food intake.

Adrenergic alpha-Agonists

Effects of the alpha 1-adrenergic agonist cirazoline on locomotion and brown adipose tissue thermogenesis in the rat.

Anorexia is induced by injection of alpha 1-adrenergic receptor agonists into the hypothalamic paraventricular nucleus (PVN) in rats. Of the agonists tested to date, cirazoline is the most potent when administered either into the PVN or systemically. The present experiments assess the effects of systemically administered cirazoline, at doses that suppress food intake, on dopamine and norepinephrine systems as evident in locomotion and stereotypy and in the induction of brown adipose tissue (BAT) thermogenesis. In Experiment 1, adult male rats were treated with either vehicle (0) or 0.05, 0.1, 0.2 or 0.4 mg/kg cirazoline (IP) prior to 30 minutes assessment of horizontal and vertical locomotion and stereotypy in Omnitech activity chambers. Horizontal activity and stereotypy were significantly suppressed at 0.05 mg/kg cirazoline but these effects waned at higher cirazoline doses. In Experiment 2, interscapular BAT temperature in adult male rats was monitored for 30 minutes after injection (IP) of either vehicle or 0.4 mg/kg cirazoline. Cirazoline, at 0.4 mg/kg did not influence BAT temperature whereas a positive control treatment (phenylpropanolamine: 40 mg/kg) rapidly increased BAT temperature during a 15 minute period after injection. These results suggest that cirazoline-induced anorexia is not the result of competing motor responses and that this drug, at a dose that produces maximal suppression of feeding, does not alter BAT thermogenesis.

Adipose Tissue, Brown

Effects of adrenalectomy and deprivation condition on food intake after phenylpropanolamine or clonidine.

alpha-Adrenergic receptors within the paraventricular hypothalamus (PVN) modulate feeding such that activation of alpha 2-adrenoceptors by drugs such as clonidine (CLON) increase feeding; whereas activation of alpha 1-adrenoceptors by drugs such as phenylpropanolamine (PPA) suppress feeding. Prior studies suggest that the feeding-stimulatory effect of alpha 2-adrenergic activation is a function of drug dose as well as the deprivation condition and adrenal status of the animal. Specifically, CLON's effects on feeding are greatest at low doses in food-satiated adrenally intact rats. Whether a similar profile is produced by alpha 1-adrenoceptor agonists such as PPA has not previously been explored. Thus, the present study provides a comparison of the effects on food intake of drug dose, deprivation condition, and adrenalectomy induced by these alpha 2- and alpha 1-adrenergic drugs. Accordingly, both adrenalectomized (ADX) as well as sham-control (SHAM) adult male rats underwent a series of 1-h feeding tests following administration of PPA (5, 10, 20 mg/kg, IP) as well as CLON (0.0125, 0.025, 0.05, 0.1 mg/kg, IP) under both deprived and nondeprived testing conditions. The results suggest that the deprivation condition, but not the surgical condition (ADX vs. SHAM), exerts the greatest overall effect on food intake following administration of alpha-adrenergic drugs.

Adrenalectomy

Reversal of cirazoline- and phenylpropanolamine-induced anorexia by the alpha 1-receptor antagonist prazosin.

Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha 1-adrenoceptors, with some alpha 2-adrenergic activity. Microinjections of PPA, as well as the alpha 1-adrenergic receptor agonists cirazoline, methoxamine, and 1-phenylephrine, into rat paraventricular nucleus (PVN) suppress feeding. The present study further evaluates the alpha 1-adrenergic basis of PPA-induced anorexia by examining the effects of systemic injections of the alpha 1-adrenergic antagonist prazosin (PRAZ, 2 and 5 mg/kg, IP) on the anorexia induced by systemic injections of PPA (5, 10, and 20 mg/kg, IP), as well as cirazoline (0.05, 0.1, and 0.2 mg/kg, IP). Although neither PRAZ dose alone altered food intake in the present study, 2 mg/kg PRAZ effectively reversed the feeding-suppressive effects of both PPA and cirazoline. These results strongly support the hypothesis that alpha 1-adrenoceptor stimulation mediates the anorexia induced by drugs such as PPA and cirazoline.

Adrenergic alpha-Agonists

Microinjection of the alpha 1-agonist methoxamine into the paraventricular hypothalamus induces anorexia in rats.

Adrenergic receptors within the paraventricular hypothalamus (PVN) play a prominent role in the control of food intake: stimulation of alpha 2-adrenoceptors induces food intake whereas stimulation of alpha 1-adrenoceptors suppresses food intake. This study further examines the role of PVN alpha 1-adrenoceptors by examining the effects on food and water intake of the alpha 1-adrenergic agonist methoxamine (100, 200, 400 nMol) microinjected into the rat paraventricular hypothalamus. Methoxamine suppressed food intake but not water intake. Doses of 100, 200, and 400 nMol methoxamine suppressed food intake by 47%, 64%, and 96%, respectively. These results further confirm the hypothesis that administration of alpha 1-agonists into the PVN acts to significantly suppress food intake; an action that is in opposition to the facilitory effects of alpha 2-adrenergic agonists on food intake.

Animals

Reversal of phenylpropanolamine anorexia in rats by the alpha-1 receptor antagonist benoxathian.

Phenylpropanolamine (PPA) is a phenethylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. Direct injections of PPA as well as the alpha-1 agonist 1-phenylephrine into rat paraventricular nucleus (PVN) suppress feeding. In the present study, we evaluate the hypothesis that systemic PPA acts within the PVN on an alpha-1 receptor population to suppress feeding. Accordingly, adult male rats were prepared with a unilateral guide cannula aimed at the PVN. Microinjection of the alpha-1 adrenergic receptor antagonist benoxathian (0, 2.5, 5.0 or 10.0 nmol) into the PVN was found to have no effect on baseline feeding behavior. Microinjection of 10.0 nmol benoxathian into the PVN completely reversed the anorexia induced by 2.5, 5.0 or 10.0 mg/kg PPA (IP), yet did not alter the hypodipsia produced by PPA. These data strongly suggest that PPA anorexia is mediated by an alpha-1 adrenergic satiety mechanism within the PVN.

Adrenergic alpha-Antagonists

Suppression of feeding induced by phenylephrine microinjections within the paraventricular hypothalamus in rats.

Rats were treated with the alpha-2 agonist clonidine (4, 20 and 50 nMol) and with the alpha-1 agonist 1-phenylephrine (50, 100, 200 and 400 nMol). Phenylpropanolamine (PPA) is a phenythylamine anorectic drug that exerts direct agonist effects predominantly on alpha-1 adrenergic receptors, with some alpha-2 adrenergic activity. We recently reported that injection of PPA significantly suppressed feeding in rats. Prior studies have noted that into the paraventricular hypothalamus (PVN) microinjections of the alpha-2 adrenergic receptor agonist clonidine into the PVN induced feeding behavior in satiated rats. However, the effect on feeding of administration of alpha-1 adrenergic agonists within the PVN remains unknown. In the present study, unilateral guide cannulae aimed at the PVN were surgically implanted in adult male rats. In an initial 60 min feeding test conducted under free-feeding ("non-deprived") conditions, each rat was found to eat significantly more food after injection of 25 nMol norepinephrine (NE) into the PVN. In subsequent tests, the feeding increased significantly to 4 nMol clonidine; however, feeding was suppressed by 50 nMol clonidine. Food intake after 20 nMol clonidine was not significantly different from that recorded after vehicle. In contrast, phenylephrine (100-400 nMol) reliably suppressed feeding behavior. In the final phase of the study, the rats ate significantly less food after injection of 160 nMol PPA into the PVN but consumed significantly more food after a final injection of 25 nMol NE into the PVN. These results suggest that the anorexic action of PPA may be linked to activation of alpha-1 adrenergic receptors within the PVN.

Analysis of Variance

Caffeine exposure sensitizes rats to the reinforcing effects of cocaine.

The present study examined the effect of pre-exposure to a moderate dose of caffeine (20 mg kg-1) on the acquisition of self-administration of cocaine (0.125 mg kg-1/infusion or 0.25 mg kg-1/infusion) in the rat. Rats pre-exposed to caffeine acquired self-administration more rapidly. Furthermore, sensitization to cocaine's reinforcing effects was accompanied by an increase in the neurochemical response of the mesolimbic dopamine system to an acute injection of cocaine (10 mg kg-1, i.p.) as measured by in vivo microdialysis. Thus, the data suggest that exposure to caffeine can increase the reinforcing effects of cocaine, possibly via an enhanced response to the mesolimbic dopamine system.

Animals

Diurnal variation of phenylpropanolamine anorexia in rats.

An examination of the effects of the diurnal cycle on phenylpropanolamine (PPA) anorexia was conducted using two groups of rats, differentiated on the basis of time (Night or Day) of drug injection (0, 10, 20, or 30 mg/kg PPA). The results demonstrate that PPA, over a range of doses, has greater anorectic potency during the dark phase of the diurnal cycle. Moreover, the effect of PPA on water intake was not influenced by the diurnal cycle, suggesting that the diurnal effect was limited to the inhibitory action of PPA on feeding. Other studies are cited which, combined with the present results, suggest that the diurnal cycle may modulate feeding control processes, and that the impact of an anorectic agent such as PPA on feeding behavior may be, in part, a function of the diurnal cycle.

Animals

Conditioned taste reactivity in rats after phenylpropanolamine, d-amphetamine or lithium chloride.

That an aversive property of phenylpropanolamine (PPA) in part contributes to its anorexic capacity is suggested by the demonstration of conditioned taste avoidance to PPA doses ranging from 10-40 mg/kg. In order to further evaluate the putative aversive property of PPA, the present experiment compared the effects of PPA on multiple measures of aversion (chin rubs, gaping) in the taste reactivity (TRT) paradigm with those produced by the classic agent lithium chloride and by amphetamine. Male rats were infused via an intraoral cannula with 0.5 M sucrose followed by injection with either vehicle, 127 mg/kg lithium chloride (LiCl), 1.5 or 3.0 mg/kg amphetamine or by 10, 20 or 40 mg/kg PPA. LiCl and 40 mg/kg PPA induced significant chin rub responses during conditioning but only the aversive response induced by 40 mg/kg PPA persisted during extinction trials. In contrast, lower doses of PPA (10 mg/kg, 20 mg/kg) were not aversive in the TRT paradigm. These results suggest that an aversive component is not contributing to anorexia induced by PPA within the dose range of 10-20 mg/kg, but that higher doses may further suppress appetite via an aversive action.

Animals

Effects of paraventricular hypothalamic microinjections of phenylpropanolamine and d-amphetamine on mash intake in rats.

The present experiment compared the effects of unilateral microinjections (40, 80 and 160 nmol/0.5 microliter) of phenylpropanolamine (PPA: d,l-norephedrine) and d-amphetamine sulfate within the paraventricular hypothalamus (PVN) on consumption of a palatable sweetened-mash diet in 15-hour food-deprived adult male rats. Intracranial microinjections were administered 5 minutes prior to each 30-minute feeding trial. PPA, at a dose of 160 nmol, suppressed feeding by 42%, whereas a similar dose of amphetamine suppressed feeding by 49%. Amphetamine or PPA doses of 40 and 80 nmol were without significant effect on feeding behavior. A relatively high dose of 160 nmol amphetamine was required to suppress feeding after injection into the PVN whereas much lower amphetamine concentrations are required to suppress feeding after injection into the perifornical hypothalamus. In contrast, PPA has some anorexic activity within the PVN but not within the perifornical hypothalamus.

Animals

Anthropometry of Algerian women.

An anthropometric study was carried out in Algeria between March 1986 and September 1987. A set of body dimensions were taken from a sample of 666 Algerian female subjects, age range 16-65 years. The subjects were selected randomly and covered a mix of occupational groups. The measurements were taken as part of a fuller study, and were chosen for their relevance to furniture design and the domestic workplace layout. Results are presented, discussed, and compared with those of other female populations.

Adolescent

The effect of backrest inclination, lumbar support and thoracic support on erector spinae muscles when lifting.

The effect of backrest inclination, lumbar support and thoracic support on the erector spinae muscle when lifting while sitting has been investigated. It was found that the lowest values of the iEMG of the back muscle were obtained when: (1) the lumbar support was positioned +4 cm forward, the thoracic support inclined to +10 degrees and the backrest inclination at 110 degrees; (2) the lumbar support was positioned +4 cm forward, the thoracic support inclined to +10 degrees and the backrest inclined to 100 degrees; (3) the lumbar support was positioned +1 cm forward, the thoracic support inclined to +10 degrees and the backrest inclination 110 degrees; (4) the backrest was inclined to 100 degrees the thoracic support inclined to 10 degrees and the lumbar support 1 cm forward; (5) the backrest inclination and lumbar support were both increased; (6) the thoracic support and the backrest inclination were both increased.

Adolescent