Peak blood alcohol prediction: an empirical test of two computer models.

OBJECTIVE: Two computer programs (Computerized Blood Alcohol Calculator and Blood Alcohol Content Estimator) were compared for reliability in predicting peak blood alcohol concentration (BAC). METHOD: Subjects were middle-aged volunteers (N = 40; 20 men, 20 women) who each consumed a constant amount of alcohol (40 ml of 95% alcohol or 30 g ethanol) prior to undergoing breath testing to determine peak BAC. The observed BACs were compared with the predicted BACs obtained with each of the computer programs. RESULTS: The Computerized Blood Alcohol Calculator provided marginally better BAC predictions than did the Blood Alcohol Content Estimator. However, both computer models seriously underestimated the peak BACs for this group of subjects. CONCLUSIONS: Results are discussed with particular reference to the need for additional studies of age, gender, and body composition in predicting peak BACs for heterogeneous subject groups.

Total body water and peak alcohol concentration: a comparative study of young, middle-age, and older females.

A search of the alcohol research literature reveals that very little experimental work has been done to describe the effects of alcohol in older females. In the present study, the effects of age and body water volume on the resultant peak alcohol concentration were observed for females ranging in age from 21 to 81. The peak alcohol concentration was estimated by breath testing in three groups of female volunteer subjects: young (21 to 25 years old), middle-age (35 to 47 years old), and older (>60 years old) after ingestion of 30 g of alcohol. Bioelectrical impedance analysis and anthropometric equations were used to estimate total body water, percent body water, and percent body fat for each subject. Significantly higher blood alcohol concentrations were obtained in older females [mean blood alcohol concentration (+/-SD) = 0.0975+/-0.018], compared with younger females (0.0818+/-0.016 and 0.0811+/-0.012). The results suggest, however, that this effect cannot be fully explained by the notion that older persons have a smaller body water volume. Particular attention is paid to the difference between total body water in liters and body water expressed as a percentage of body weight. Evidence is offered to demonstrate that percent body fat is not a determinant of the blood alcohol level an individual will attain. The findings are discussed with particular reference to the lack of experimental work involving older females and alcohol.

Conditioned taste aversion in rats induced by the alpha 1-adrenoceptor agonist cirazoline.

Recent studies have indicated that alpha 1-adrenoceptor agonists such as phenylpropanolamine (PPA), cirazoline, amidephrine, and SK&F-89748 suppress food intake in rats. These compounds activate alpha 1-adrenoceptors within the paraventricular hypothalamic nucleus (PVN) and may excite efferent fibers that inhibit feeding. Studies of the effects of alpha 1-agonists suggest a specificity for feeding behavior, but no study to date has evaluated whether these agonists may suppress feeding behavior by the induction of malaise. Accordingly, the present experiment examined the ability of systemically administered cirazoline (0.1, 0.2, and 0.4 mg/kg, IP) to induce conditioned taste aversion (CTA) to a saccharin solution. Significant CTA was noted for 0.2 and 0.4 mg/kg cirazoline but not for 0.1 mg/kg cirazoline, compared to a vehicle treatment. The ED50 for cirazoline-induced aversion was computed to be 0.3 mg/kg, which contrasts with an ED50 value of 0.09 mg/kg for the effect of cirazoline on food intake (computed in other studies). More importantly, a 0.1 mg/kg dose of cirazoline, which is slightly greater than that of the ED50 value for suppression of feeding, did not induce significant CTA in the present study. These results suggest that malaise is not a prominent factor in the suppressive activity of cirazoline on food intake and advocate the use of cirazoline as an effective appetite suppressant.

An assessment of the involvement of paraventricular hypothalamic alpha 2-adrenoceptors in phenylpropanolamine anorexia.

Systemic injection of phenylpropanolamine (PPA), an alpha 1-adrenergic receptor agonist with some activity at alpha 2-adrenergic receptors, suppresses food intake in rats. However, only limited information is available as to the effect of intracranial PPA injections on food and water intake. In Experiment 1, microinjection of PPA (80-240 nM) into the hypothalamic paraventricular nucleus (PVN) induced a dose-dependent suppression of feeding (ED50 = 181 nM) but was without significant effect on water intake. Experiment 2 evaluated the effect of systemic PPA on paraventricular hypothalamic norepinephrine (NE) levels. Rats were treated with either vehicle or 20 mg/kg (IP) PPA prior to a 100-min period in which extracellular NE within the PVN was monitored via an indwelling microdialysis probe. Systemic injection of PPA suppressed extracellular NE level within PVN by approximately 70%, an action consistent with stimulation by PPA of a presynaptic alpha 2-adrenergic autoreceptor. Experiment 3 evaluated whether the alpha 2-adrenergic activity of PPA contributes to its feeding-suppressive action. Unlike prior results using the alpha 1-antagonist benoxathian, PVN microinjection of the alpha 2-antagonist rauwolscine in Experiment 3 of the present study failed to block systemically induced PPA anorexia. These results further support the contention that PVN alpha 1-adrenergic receptors suppress feeding and suggest that PPA's alpha 2-adrenergic effects do not modulate the anorexic action of PPA.

Effects of intra-PVN injections of d- and l-norephedrine on feeding in rats.

Phenylpropanolamine (PPA) is thought to inhibit feeding by activation of alpha 1-adrenergic receptors within the paraventricular hypothalamus (PVN). Systemic injections of the PPA component enantiomers, d- and l-norephedrine (NEP), result in differential suppression of feeding (l-NEP more potent than d-NEP). Whether the norephedrine racemates induce differential anorexia subsequent to injection into the PVN is unknown. In the present study, adult male rats received intra-PVN injections of the d- and l-norephedrine enantiomers (0, 80, 160, and 240 nmol). Significantly greater anorexia was obtained for l-NEP relative to d-NEP. These results document a stereospecific effect of the norephedrine enantiomers within the PVN in inhibiting food intake and suggest that the interaction of these enantiomers with PVN alpha 1-adrenoceptors may mediate the similar difference in potency noted for systemic injections of d- and l-norephedrine.

Modulation of feeding by hypothalamic paraventricular nucleus alpha 1- and alpha 2-adrenergic receptors.

Noradrenergic receptor populations within the paraventricular hypothalamus (PVN) modulate feeding. Satiated rats exhibit enhanced feeding subsequent to activation of alpha 2-adrenergic receptors within the PVN induced by exogenous infusion of either norepinephrine (NE) or clonidine (CLON). The feeding-stimulatory effect of alpha 2-adrenergic agents presumably reflects an inhibitory action on receptors located on medial hypothalamic "satiety" cells. Adrenergic receptors of the alpha 1-subclass have been identified within the PVN which are excitatory and which may function to suppress food intake. Microinjection into rat PVN of various alpha 1-adrenergic agonists including cirazoline, methoxamine, phenylpropanolamine and phenylephrine suppress feeding; an effect that is reversed by pretreatment with alpha 1-adrenergic receptor antagonists. The present review argues that alpha 1- and alpha 2-adrenoceptors within brain and specifically within the PVN are organized in an antagonistic fashion and that the effects of various adrenergic agonists on feeding may reflect the degree to which these agonists act at alpha 1- and alpha 2-adrenoceptors as well the relative balance of these receptors and their activity within the PVN.

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.

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.

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.

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.

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.

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.

Effects of circadian cycle and time of testing on drug-induced anorexia in rats.

Based on the results from a previous study conducted in our laboratory, the present experiment sought to replicate the finding that the magnitude of the anorexic effect of phenylpropanolamine (PPA) in rats is greater during the early dark phase than the early light phase of the circadian cycle. Moreover, the present study included two additional anorectic drugs, amphetamine and fenfluramine, as well as additional testing times in the middle of the respective phases of the circadian cycle. For the 1h feeding tests, all three anorectic drugs demonstrated a significant dose-dependent phase (Light/Dark) effect such that all three agents induced greater anorexia during the dark phase. The significance of the dark phase testing was also apparent after 4h of testing for PPA and amphetamine, but not for fenfluramine. Furthermore, during the 1h tests, PPA and amphetamine, but not fenfluramine, demonstrated significant test time interactions such that the greatest magnitude of anorexia was observed during the middle of the dark phase. The present data are intriguing in that the anorexic effects of these three drugs, which are believed to operate via three distinct neurochemical mechanisms, are modulated by the circadian cycle in a similar fashion during a 1 h feeding trial. Thus, the results of this study indicate that one salient factor (i.e. time of testing within the circadian cycle) may, in part, contribute to the variability often observed in feeding studies using different experimental protocols.

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.

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.

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.

Novel versus familiar ethanol: a comparison of aversive and rewarding properties.

Rats were given a series of the conditioning trials during which sucrose solution was paired with ethanol which had previously been experienced on 0, 3, or 9 occasions. On each conditioning trial, the rats received a Taste Reactivity Trial, a Taste Avoidance Trial, and a Place-Conditioning Trial. After the rats had received 4 conditioning trials, they were given a Conditioned Place Preference Test, a Taste Reactivity (TR) Test, and a Conditioned Aversion Extinction Test. Only the group conditioned with novel ethanol demonstrated aversive TR responses, although all CS + groups eventually demonstrated suppressed ingestive TR responses and enhanced neutral TR responses. Familiarization attenuated, but did not eliminate, ethanol-induced CTAs. There was no evidence of place conditioning.

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.

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.

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.