Prog. NeumPsychophammcol6 Biol. Psychiot. 1883. Vol. 7, pp. 301-304 Printed in Great Britain. AU ri3ht.s resewed.

0278-3346/83 $0.00 + 30 Copyrtght 0 1933 Pergamon Press Ltd.

THE EFFECTS OF p-p- AND PHENYLETHANOLAMINE ON WATER INTAKE IN RATS: A TEMPORAL ANALYSIS

A.J. GREENSRAW, J. BROADBENT AND A.A. BOULTON

Psychiatric Research Division, University of Saskatoon, Saskatchewan, Canada

(Final form, July 1983)

Abstract

Greenshaw, A.J., J. Broadbent and A.A. Boulton: The effects of S-phenylethylamine and

Saskatchewan,

phenylethanolamine on water intake in rats: a temporal analysis. Prog. in Neuro-psycho- pharmacol. 6 Biol. Psychiat. 1983, 7(4-6):801-804. 1. Male Wistar rats were adapted to a restricted access schedule of water intake. 2. For each animal overall water intake (ml) and number of licks per minute were measured

over the period of access to water. 3. The effects of various doses of S-phenylethylamine and of phenylethanolamine were

assessed in separate groups of animals. 4. In terms of effects on overall consumption the two amines were equipotent in suppress-

ing water intake. The local analysis revealed, however, that S-phenylethylamine was more potent, but had a much shorter duration of action than phenylethanolamine.

Keywords: B-phenylethylamine, hypodipsia, licking, phenylethanolamine, temporal analysis, water-intake

Abbreviations: S-phenylethylamine (PE), phenylethanolamine (PEOH)

Introduction

S-phenylethylamine (PE) is the parent compound of a number of potent anorectic agents such as d-amphetamine and fenfluramlne. PE, a trace amine that occurs naturally in the mammalian central nervous system (Durden et al 1973) is itself a potent anorectic agent (Mantegazza and Riva 1963, Dourlsh and Boulton 1981). However, in contrast to the observa- tion that d-amphetamine and fenfluramine may reduce water consumption In rats (Eolteman and Jewett 197-i, Soulairac and Soulairac 1970), it has been reported that this amine does not significantly affect water consumption in the rat (Barr et al 1979, Dourish and Boulton 1981, Thornton 1980). There have, however, been no reports of studies specifically direct- ed to the investigation of effects of PE on drinking. The present study was therefore con- ducted in order to assess the effects of a wide range of doses of PE and the structurally similar endogenous amine phenylethanolamine (PEOH) on water consumption in waterdeprived rats. In the present study a temporal analysis of drinking was conducted In an attempt to reveal any effects that PE and PIIOU may have on local patterns of licking In this species.

801

802 A.J. Greenshaw et al.

Materials and Methods

Thirteen male Wistar rats weighing between 200 and 250 g served as subjects; they were group housed with free access to food. Temperature was maintained at 20-22'C and the lights operated on a 12 h light/dark cycle (lights on at 6:00 a.m.). Water was available according to the experimental protocol. A metal test chamber (Coulborn Insts. ElO-10) equipped with a drinking spout recessed into the centre of the front wall was used. The spout was connected to a 50 ml burette. An infra-red photosensor located between the wall of the test chamber and the drinking spout was connected to a Commodore 4016 microcomputer that served to record each lick-interruption of the photo-beam in local time intervals throughout the test sessions.

The subjects were each given access to tap water (20-22°C) in the test chamber for a period of 30 minutes per day. The total volume of water consumed was measured to the near- est 0.1 ml, concurrently, the number of licks emitted during each minute was recorded to provide an analysis of the temporal distribution of licking. After ten days adaptation to this drinking regimen the effects of several doses (3.24-41.7 mg/kg> of PE hydrochloride and of PEOH were investigated. The present logarithmic range of doses was chosen in order to provide a detailed dose-response analysis. The compounds were dissolved in isotonic saline and administered IP in a volume of 1 ml/kg two minutes prior to testing. Each animal received each dose once, the doses being administered in a mixed order. Separate groups of animals were used to assess the effects of PE (n=5) and of PEOH (n=8). At least three sessions were run between each drug administration session. Equivalent volumes of isotonic saline were administered on all non-drug days.

Results

The effects of PE and of PEOH on mean water intake are displayed in Fig. 1. The two groups of animals consumed an average of 14-15 ml over the control days immediately preced- ing drug administration. Administration of PE and of PEOH resulted in a dose-dependent

4

C 3.24 5.4 9.0 15.0 29.0 41.1

20

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s 0

4

, 1

C 3.24 5.4 9.0 15.0 25.0 41.1

B-PHENYLETHYLAMINE mg/kg PHENYLETHANOLAMINE mg/kg

Fig. 1. The effects of PE and PEOH on water intake during the 30 min test period. The data point at C represents the overall group mean for water intake averaged over each day immediately preceding administration of PE. The data points for each dose of PE represent the average intake for the group after each PE treatment. Vertical bars are standard deviations. The values for 25.0 and 41.7 mg/kg are significantly different from C (p < 0.01).

Effects of phenylalkylamines on water intake 803

depression of water intake. These effects were observed with the higher doses (25, 41.7

mg/kg). Repeated measures ANOVA revealed that the effects of PE and of PEON were etatietl- tally significant [P (5,24) = 29.94, p < 0.01; F (6,42) = 7.20, p < 0.011. Multiple comparisons using the Newman-Keuls test ( = 0.01) revealed that water intake after the 25.0 and 41.7 mg/kg doses was significantly less than that of the average control value.

The effects of PE and PEOH on the distribution of licking over the session are displayed in Fig. 2. The upper panel of these figures shows the average number of licks emitted dur- ing each minute of the session for each group of subjects after administration of Isotonic saline; the average rate of licking for the group declined progressively over the session. The lower panels of these figures illustrate the effects of each dose of PE and of PEOH respectively on this pattern of licking. For clarity the control data from the upper panels are displayed against the effect of each dose of PE and of PEOH respectively in the lower panels of the figures. From these figures it is evident that, at doses of 15.0 mg/kg and above, administration of PE resulted in a disruption of licking in the first minutes of the session. After administration of PE at 15.0 mg/kg this disruption was only apparent for approximately the first seven minutes of the session. With the higher doses of PE the

initial disruption of licking was of greater duration, lasting for approximately 11 and 16 minutes for the 25.0 and 41.7 mg/kg treatments respectively. With these doses of PE there was an increase in the average number of licks emitted after recovery from the initial disruption of drinking Induced by the drug. With the 15.0 mg/kg treatment this recovery was early enough for the animals to compensate for the decreased water intake early in the session (as shown by the water intake data displayed in Fig. 1). At 25.0 and 41.7 mg/kg,

however, the duration of this initial disruption of drinking resulted in a net decrease in water intake (see Fig. 1) despite the apparent recovery of licking after these doses In the latter part of the session. With PEOH (Fig. 2) the onset of the disruption of licking was slower and although the duration of action of PEOH was longer, licking was not completely inhibited by any of the doses tested. These effects were statistically significant [PE F

(5,24) - 15.25; time F (29,696) - 4.06; interaction F (145,196) = 8.78; PEOH F (6,49) = 6.30; time F (29,1421) = 28.67; interaction F (174,142l) = 2.18, p < 0.01 in each case.

SCALE 0*300

PE w/kg

SCALE 0+300

PEOH m&g

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41.7 2

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1 10 20 30

MINUTES

3.24

I 5.4

I 9.0

I 15.0

25.0

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Fig. 2. The effects of saline and of each dose of PE and of PEOH on the average number of licks emitted by the group of rats during each minute of the test sessions. For ease of comparison the performance of the group after saline (dotted line - upper panels) is euperimposed on the groups performance after administration of each dose of PE (solid lines - lower panels).

804 A.J. Greenshaw et al.

In contrast to previous reports (Barr et al 1979, Dourish and Boulton 1981, Thornton 1980), the present results clearly demonstrate that PE and PEOH show the hypodipsic proper- ties of PE derivatives such as amphetamine. The transient nature of this effect of PE, as revealed by the analysis of licking, may be attributed to the rapid breakdown of PE by monoamine oxidase. The longer duration of action of PEOH indicates that this amine may be less readily oxidised in vivo. -- Nevertheless, in contrast to reports of hypophagia, admini- stration of PE (Dourish and Boulton 1981), the transient hypodlpsic effect of PE appears to correspond to the duration of the syndrome of stereotyped motor activity elicited by this compound (Dourish et al 1983). The present hypodipsic effects of PE are, therefore, more likely to represent interference with drinking than a specific effect on mechanisms under- lying the control of water intake.

Acknowledgements

The continuing financial support of Saskatchewan Health is gratefully acknowledged.

References

BARR, G.A., GIBBON, J.L. and BRIDGER, W.H. (1979) A comparison of the effects of acute and subacute administration of -phenylethylamine and i-amphetamine on mouse-killing behavior of rats. Pharmacol. Biochem. Behav. 11: 419-422.

DOURISH, C.T. and BOULTON, A.A. (1981) The effzts of acute and chronic administration of -phenylethylamlne on food intake and body weight in rats. Prog. Neuro-Psychopharmacol. 5: 411-414.

DOiiRISH, C.T., GRBENSHAW, A.J. and BOULTON, A.A. Deuterium substitution enhances the effects of -phenylethylamine on spontaneous motor activity in the rat. Pharmac. Biochem. Behav. (in press).

DURDEN, D.A., PHILIPS, S.R. and BOULTON, A.A. (1973) Identification and distribution of -phenylethylamine in the rat. Can. J. Blochem. 51: 995-1002.

HOLTZMAN, S.G. and JEWBTT, R.E. (1971) The role ofbrain norepinephrine in the anorexic effects of dextroamphetamine and monoamine oxidase inhibitors in the rat. Psychopharmacologla 22: 151-161.

MANTEGAZZA, P. and RIVK M. (1963) Amphetamine-like activity of -phenylethylamine after a monoamine-oxidase inhibitor in viva. J. Pharm. Pharmacol. 15: 472-478.

SOULAIRAC, A. and SOULAIRAC, M.-cm70) Effects of ampheta&e-like substances and L-Dopa on thirst, water intake and diuresis. In: Costa, E. and Garattini, S. (eds) Amphetamines and related compounds. Raven Press, New York, pp 819-837.

THORNTON, E.W. (1980) Effect of -phenylethylamine on social dominance in rat dyads during competition for water. IRCS Medical Science: Psychology and Psychiatry 8: 860-861.

Inquiries and reprint requests should be addressed to:

Dr. A.J. Greenshaw Psychiatric Research Division CMR Building, University of Saskatchewan Saskatoon, Saskatchewan S7N OWO Canada