Seasonal variation in opioid modulation of feeding in the 13-lined ground squirrel

Physiology &Behavior.Vol 37. pp 5-9 Copyright©Pergamon Press Ltd. 1986 Printed in the U S A

0031-9384/86 $3 00 + 00

Seasonal Variation in Opioid Modulation of Feeding in the 13-Lined Ground Squirrel STEVEN

E

NIZIELSKI, ALLEN S LEVINE, 1JOHN E KENT A HALL AND BLAKE A GOSNELL

MORLEY,

Neuroendocrme Research Laboratory, VA Medtcal Center, Mmneapohs, M N Department of Food Sctence and Nutrition and Medicine, Untverstty of Minnesota St Paul-Mtnneapohs, M N Geriatric Research Education and Clinical Center, VA Medical Center, Sepulveda, CA and Department o f B:ology, University of Wtsconsm-Stevens Point, Stevens Point, WI R e c e i v e d 25 S e p t e m b e r 1985 NIZIELSKI, S E , A S LEVINE, J E MORLEY, K A HALL AND B A GOSNELL Seasonal vartatum m oplotd modulat:on of)eedmg :n the 13-hned ground squ:rrel PHYSIOL BEHAV 37(1) 5-9, 1986 --Oplolds are well recograzed to modulate mgestzve behaviors m a variety of species To study the potentml role of op~o~ds m the alteration of mgestwe behaviors that occur prior to h~bernat~on, we have administered opiate agomsts and the antagomst, naloxone, to the 13-hned ground squirrel (Spermophdus trtdecemhneatus) during permds when they were hyperphaglc and hypophaglc Naloxone consistently reduced feeding dunng both phases of the feeding cycle Hypophaglc animals, however, were 10 times more sensmve to the effects of naloxone The effect of the opmte agomsts (morphine and butorphanol, 1 and 10 mg/kg) on feeding also vaned between seasons The low dose of morphine produced a shght, but slgmficant increase in feeding at one hour m hyperphaglc animals, whde the h~gh doses tended to decrease feeding When admlmstered to hypophaglc ammals, feeding was decreased by both doses of each agonlst Immunoreact~ve (IR)-dynorphm levels m the cortex, hypothalamus and strmtum were higher dunng the hypophaglc phase compared w~th the hyperphagtc phase These data indicate that the 13-hned ground sqmrrel possesses an opmte sensitive feeding system which ~s affected by season Feeding

Oplotds

Ground squirrel

Hibernator

A L T H O U G H it has been estabhshed that the endogenous opiates play a role in the regulation of appetite in numerous species, feeding in other species has failed to respond to the administration of either opiate antagonists or agonists Generally, the opiate antagonists are capable of reducing food consumption under a variety of conditions, while various opiate agonists have been effective at increasing food intake in rats and mice [27] The golden hamster, however, was one of the first animals whose feeding appeared to be unaltered following the administration of either opiate agonists or antagonists [15,16] Being that the golden hamster is a hibernating animal we wished to see if this apparent lack of an opiate sensitive feeding system would be common among hibernators, or other animals which show similar seasonal periods of hyper and hypophagm commonly found in hibernating species [28] In addition, very little data has been accumulated on the effects of opiate agomsts in species other than rats and mice In hght of the suggestion that the endogenous opiate s may be key factors m the mediation of various physiological and behavioral responses which are important for species survl-

Dynorphm

Spermophdu~trtde~emhneatu~

val [16], we are interested in observing the effect of opiate agonists on feeding in various species Previously we reported that feedmg in the racoon was resistant to the effects of opiate receptor blockade, while the woodchuck (a hibernator) did decrease feeding following the administration of naloxone [30] In this paper we present the effects of the opiate antagonist naloxone and the opiate agonIsts morphine and butorphanol tartrate on feeding during both the hyper and hypophaglc phases of the feeding cycle in another hibernator, the 13-hned ground squirrel Morphine is a prototype mu agonist whereas butorphanol tends to preferentially stimulate the kappa receptor Our previous studies in the rat [12] have found butorphanol to be a more effective feeding stimulator than morphine in that species As we have accumulated much evidence that dynorphln, the endogenous kappa hgand, plays an important role in feeding modulation [24], we also measured the levels of ir-dynorphln in the C N S during the hypo- and hyperphaglc periods METHOD The animals used in these experiments were juvenile,

JRequests for repnnts should be addressed to Allen S Levme, Ph D , VA Medical Center (111P). 54th St and 48th Ave S , Minneapolis. MN 55417

6

NIZIELSK1 E] A L

male and female, 13-hned ground sqmrrels born m the laboratory from wdd female ground sqmrrels trapped near Madison. WI They were housed individually m suspended cages and prowded with Purina rat chow and sunflower seeds ad hb A 12 hour hght/dark schedule was malntamed and the room was kept at approximately 23°C The response of food consumption to opiate agomsts (morphine and butorphanol tartrate) and the opmte antagomst naloxone were measured dunng both the hyperphaglc and hypophaglc phases of the feeding cycle Trmls at each phase were begun with opmte naive animals Our ammals were hyperphaglc during July and August, with average dally food retake being 115 g/kg or more The hypophaglc phase of the feeding cycle began in September and continued through November, with average dally food retake being less than 20 g/kg b wt Average food retake was determined from five ammals whose food consumption (chow only) was regularly monitored Food was available ad hb prior to the mtrapentoneal (1P) mjecUon of the opiate agonlsts (morphine and butorphanol, 0, 1 and 10 mg/kg) whde the opiate antagonist naloxone (0, 0 05, 0 1, 1 and 10 mg/kg) was administered intramuscularly following 20 hours of food deprivation Physiological sahne served as a vehicle for each drug A weighed portion of rat chow was presented to the animals immediately following the admmlstraUon of the agomsts and 15 minutes following naloxone mjecuons Dynorphm levels were determined in four regions of the brain (anterior cortex, hypothalamus, stnatum and midbrain) during July (hyperphaglc) and October (hypophaglc) Dissections of these brain regions were camed out following the procedures of Messing et al [21] The ammals were sacnficed by decapitation and dynorphln levels were determined by radlolmmunoassay as prewously described by us [22], using a modification of the method described by Ghazarossmn et al [7] The dynorphm antibody was kindly provided by Avram Goldstem of the Addlchon Research Foundation, Palo Alto CA Data were analyzed by one-way analysis of variance A Dunnett s t-test was used as c n t e n a to determine ff individual treatment means were slgmficantly different from sahne controls A Wdcoxon-Mann-Whltney two sample test was used to analyze the seasonal brain dynorphm levels RESULTS

Admmlstratlon of naloxone in July (hyperphaglc) resulted in significant treatment effects at one and two hours (p<0 001) A 1 mg/kg dose of naloxone was the lowest dose to slgmficantly reduce food intake at this time. decreasing food consumption by 33% at one hour and 43% at two hours (p<0 05) (Fig 1) As we can see in Fig 2, naloxone was also effective at reducmg food mtake when admlmstered during the hypophaglc phase of the feeding cycle Slgmficant treatment effects were again observed at 1 and 2 hours (p<0 005), although we found that hypophaglc ammals were more senstove to naloxone than hyperphaglc ammals Hypophaglc ammals receiving 0 1 mg/kg of naloxone decreased food consumptlon by 50% at one hour (p<0 05) and 60% at 2 hours (p<0 01), while the minimum effective dose in hyperphaglc ammals was 1 mg/kg When the opmte agonlsts morphine and butorphanol tartrate were administered during August to hyperphaglc ammals, slgmficant treatment effects were observed at one (p<0 05) and six hours (p<0 01) (Fig 3) At one hour, the mcreases in feeding observed with the low dose of morphine

July

N

~ 2o

,5 to ~ o

SalN1 N1NIO SalN1NINIO I HOUR 2 HOURS

FIG I The effect ot naloxone on leedmg m the hyperphaglc 13hned ground sqmrrel I~p-005 +p-~001) Numbers refer to naloxone dose m mg/kg

September

~ o4

8~ ° z ~ l ,,o

~

Sal NO5NI NI

Sal NO5NI NI

I HOUR

2 HOURS

FIG 2 The effect ot naloxone on feeding in the hypophaglc 13-hned ground squzrrel ( ~p<0 05 +p<0 01 ) Numbers refer to naloxone dose m mg/kg

August .~ ao

-~ ~o ~ 4o ,? 2o ~ 0

SolMI MIOBI BlO 1HOUR

SolMIMIOBI BlO

SolMI MIOB1810

Sol MI MIOBI BIO

2 HOURS

4 HOURS

6 HOURS

FIG 3 q he ettect ot morphine and butorphanol m hyperphaglc 13-hned ground sqmrrels (*p<0 05 tp<0 01) Sal=sahne, M=morphme, B=butorphanol Numbers refer to dose m mg/kg

(sal, 1 2-+0 1 g, 0 1 mg/kg morphine, 1 9_+0 2 g)just achieved slgmflcance (p<0 05) Although no slgmficant treatment effects were observed at 2 or 4 hours, there was a trend for the low doses of both agonlsts tbut parucularly morphine) to increase feeding over saline controls A trend for the high dose of morphine and butorphanol to decrease food consumptton existed throughout the course of the experiment This became significant at 6 hours with butorphanol decreasing food consumption from 8 8-+0 6 g in control animals to 6 1-+0 6 g (p<0 01) When administered to hypophaglc animals, however, both doses of morphine and butorphanol consistently resulted in decreased food intake (Fig 4) Significant treatment

OPIOID M O D U L A T I O N IN THE GROUND SQUIRREL November

7 TABLE 1 SEASONAL VARIATIONIN 13-LINEDGROUNDSQUIRRELBRAIN DYNORPHIN LEVELS

Ii,o

Dynorphm (fmol/mg protein)

Sol MI MIO BI BIO

SolMI MIO BI BIO

Sol MI MIO BI BIO

2 HOURS

4 HOURS

6 HOURS

FIG 4 The effect of morphine and butorphano] in hypopbagic 13hned ground sqmrrels (*p<0 05, t p < 0 01) Sa]=sahne, M=morphme, B=butorpbanol Numbers refer to dose m mg/kg

effects were observed at 2, 4 and 6 hours (/9<0 01) whde 1 mg/kg of morphme was the only dose which d~d not slgmficantly reduce feeding at any time pomt Dynorphln levels m hypophagtc ammals were increased m the cortex (300%), hypothalamus (30%) and strmtum (150%) when compared to hyperphaglc ammals (Table 1) No slgmficant changes m dynorphm levels were noted m the mldbraln DISCUSSION AS with many other species [27], feeding is suppressed m the 13-hned ground sqmrrel following the admmlstraUon of opmte antagomsts The seasonal alteration m their sensitivity to naloxone, however, appears to be a novel finding Whde naloxone consistently reduced feeding, the effects of the opmte agomsts were more varmble Morphine and butorphanol produced only small and short-hved increases m food consumption m hyperphaglc 13-hned ground sqmrrels When administered to hypophaglc animals, however, these compounds slgmficantly decreased food consumpUon at all time points Increased sensitivity to the anorecuc effects of naloxone are known to occur under a variety of conditions The genetically obese mouse (ob/ob) and rat (fa/fa), as well as the geneUcally dmbetlc (db/db) and streptozotocm-mduced diabetic mouse show increased sensitivity to naloxone relative to controls [13,19] Elevated levels of pitmtary fl-endorphln have been shown to occur in the genetically obese ammals It has been suggested, therefore, that fl-endorphln may be involved m the chronic overeating, as well as the increased sensltlwty to naloxone observed m these animals [19] An alternative explanation suggests that elevated blood glucose levels may be modifying opiate receptors [27] Two hnes of evidence which support thts posslbdlty are (l) streptozotocm-mduced diabetic mice, which have higher blood glucose levels than genetically diabetic ammals, show an even greater sensitivity to naloxone, and (2) rats induced to eat by msuhn hypoglycemia are less sensitive to the suppresslve effects of naloxone [1 l, 14] In this study we found that early m the hypophaglc phase of the feeding cycle, ground squirrels were approxzmately ten ttmes more sensttlve to naloxone than hyperphaglc ammals Of further mterest is the fact that, hke the genetically obese and dmbetlc ammals, msuhn resistance may accompany naloxone hypersensltlwty Previously we have suggested that lnsuhn resistance may occur m 13-11ned ground sqmrrels near the end of the hyperphagtc phase of the

Cortex Hypothalamus Stnatum MIdbram n=

July (Hyperphagia)

October (Hypophagia)

Rat:~

40 _+ 2* 3201 _ 123" 457 _+ 50t 248 _+ 55

159 _+ 25 4163 _+ 129 1152 _+ 229 245 _+ 12

231 _+ 20 1216 _+ 117 273 _+ 11 314 __ 14

13

8

10

Values are means _+ S E M *Significantly dtfferent (p<0 001) between seasons by Wdcoxon-Mann-Wh~tney two sample test, tp<0 01 ~Data obtmned from ongoing studies of male Sprague-Dawley rats m our laboratory

feeding cycle [ 2 9 ] Although increased sensitivity to naloxone was found In hypophaglc animals in this study, they had.lust entered this phase and were still at peak wemght If indeed lnsuhn resistance IS occurring, it Is unhkely to have abated by this time Therefore, mechamsms which may explain the enhanced sensltlwty to naloxone m insulin resistant rats and m~ce, may also apply to the ground squirrel A more parslmonius explanation for th~s seasonal difference m sensltwlty can be offered however The sUmulus to feed ~s obviously very potent in the hyperphaglc ground squirrel, perhaps overriding normal saUety mechanisms Thus their response to any exogenously admlmstered anorexic agent, such as naloxone, may also be d~minished at this time What we may have observed, therefore, is not an enhancement of naloxone's anorexic effect during hypophagta, but a suppresslon of its effect in the hyperphaglc animal L~ke naloxone, the effect of the opiate agonlsts on feeding also varied between phases of the feedmg cycle Hyperphagtc animals tended to increase feeding following the administration of the low dose of both morphine and butorphanol In the case of morphine, this increase was significant at one hour However, when admlmstered to hypophagic animals, both doses of these agonlsts reduced feeding The increased feeding ehc~ted by the opmte agomsts m hyperphaglc 13-hned ground squirrels appears to be relatively umque, outside of rats and m~ce Pigeons have been reported to increase feeding following the mtracerebroventrlcular (ICV) injection of ostnch and human /3-endorphm [6], although morphine caused decreases in feedmg m this species [5] However, m all other species, including dogs [31], golden [16], Chinese [4], and Slbermn hamsters (unpubhshed observations) and guinea pigs [3], the opiate agomsts have had no effect, or decreased feeding The increased feedmg observed m the ground sqmrrel following morphine or butorphanol admmtstratlon were margmal however Thts ~s not surprising since ~t can be difficult to further stimulate feeding m animals which are already consuming large quantrees of food For example, morphine and the kappa agonlst, ketocyclazocme, are unable to reduce nocturnal feedmg or feeding m deprived rats [26] However, we might have expected these opmte agomsts to have amore robust stlmulatory effect on feeding m the hypophaglc ammal Instead, we

8

NIZIELSKI ET AL

f o u n d significant r e d u c t i o n s m food c o n s u m p t i o n at all time p o i n t s Th~s r e d u c t i o n o f feeding followmg the a d m i n i s t r a tion o f opiate agonlsts In t h e h y p o p h a g l c a n i m a l o c c u r r e d at a time w h e n t h e g r o u n d s q m r r e l w o u l d n o r m a l l y b e h i b e r n a t ing, and m a y be related to the sedative p r o p e r t i e s of t h e s e c o m p o u n d s A l t h o u g h casual i n s p e c t i o n did n o t reveal a n y o b v i o u s signs o f s e d a t i o n , it IS p o s s i b l e t h a t at this t~me o f the y e a r t h e s e a m m a l s are m o r e s e n s i t i v e to s e d a t i o n b y o p i a t e s T h i s suggests that the o p i a t e s m a y be i n v o l v e d in the initiation a n d / o r m a i n t e n a n c e o f h i b e r n a t i o n T h e i n c r e a s e o f b r a i n d y n o r p h l n levels in h y p o p h a g l c a n i m a l s s u p p o r t s this possibility I n c r e a s e d sensitivity to s e d a t i o n b y opiate agonlsts, c o u p l e d with i n c r e a s e d levels o f e n d o g e n o u s h g a n d m a y v e r y well lead to the d e c r e a s e d activity o b s e r v e d j u s t p r i o r to or d u n n g h i b e r n a t i o n R e p o r t s from o t h e r laboratories h a v e suggested the i n v o l v e m e n t o f t h e o p i a t e s in h i b e r n a t i o n also T h e opiate a n t a g o n i s t s , n a l o x o n e a n d n a p t r e x o n e , h a v e b e e n s h o w n to c a u s e p r e m a t u r e arousal m h~bernatlng T u r k i s h h a m s t e r s [18] a n d d o r m i c e [10], hibernating g r o u n d squirrels do n o t d e v e l o p an a d d i c t i o n to morp h i n e [1] and q u a n t i t a t i v e s e a s o n a l (but n o t q u a h t a t l v e ) d i f f e r e n c e s in the b e h a v i o r s elicited d u r i n g m o r p h i n e withd r a w a l h a v e b e e n o b s e r v e d [2] P r e l i m i n a r y results f r o m o u r l a b o r a t o r y h a v e s h o w n , h o w e v e r , that I C V injections o f d y n o r p h m a n d Ds e r - l e u - e n k e p h a h n - t h r p r o d u c e d large i n c r e a s e s m feeding m hypophag~c animals So d e c r e a s e s m feeding followmg opiate a d m i n i s t r a t i o n in h y p o p h a g l c a n i m a l s a p p e a r s to be

h m l t e d to s y s t e m i c injections A l t h o u g h it is difficult to m a k e direct c o m p a r i s o n s b e c a u s e different opiate a g o m s t s were a d m i n i s t e r e d in t h e s e studies, t h e s e results are not w i t h o u t p r e c e d e n c e P r e v i o u s l y it h a s b e e n s h o w n t h a t f e e d m g is d e c r e a s e d w h e n /3-endorphln is a d m i n i s t e r e d p e r i p h e r a l l y [9,23] but i n c r e a s e d w h e n injected 1CV [8,20] T h e s e e x p e r i m e n t s h a v e not yet b e e n r e p e a t e d m h y p e r p h a g l c a n i m a l s so it is not c l e a r at this point if t h e r e wdl be s e a s o n a l d i f f e r e n c e s o n the effect of c e n t r a l l y a d m i n i s t e r e d o p i a t e s N e v e r t h e l e s s , ~t d o e s a p p e a r t h a t the 13-hned g r o u n d s q m r r e l does p o s s e s s a n opiate s e n s i t i v e feeding s y s t e m w h i c h ~s affected by s e a s o n S e a s o n a l a l t e r a t i o n s m b r a i n d y n o r p h l n c o n c e n t r a t i o n s , sensitivity to n a l o x o n e , and the effect o f opiate agonlsts on feeding all lead to th~s conclusion T h e s e data also s u p p o r t the suggestion b y M a r g u l e s [17] t h a t e n d o g e n o u s o p i a t e s play a role in m e d i a t i n g physiological and b e h a v i o r a l r e s p o n s e s w h i c h are i m p o r t a n t for species survival F u r t h e r m o r e , t h e s e data, as well as o u r p r e v i o u s studies [29], stress the ~mportance o f c o n d u c t i n g e x p e r i m e n t s d u r i n g b o t h the h y p e r a n d h y p o p h a g l c p h a s e s o f the feeding cycle m a n i m a l s w h i c h e x h i b i t c l r c a n n u a l r h y t h m i c i t y in feeding Finally, we would like to s t r e s s that a n u m b e r of n e u r o t r a n s m l t t e r s a p p e a r to be r e v o l v e d in the m o d u l a t i o n o f food retake [25] and that ~t ~s the i n t e r a c t i o n s o f t h e s e n e u r o t r a n s m l t t e r s that a p p e a r to play a key role O u r o n g o i n g studies are, t h e r e f o r e , d~rected t o w a r d s e x a m i n i n g the role of o t h e r n e u r o t r a n s m l t t e r s m the regulation o f feedmg m the g r o u n d sqmrrel

REFERENCES 1 Beckman, A L C Llados-Eckman, T L Stanton and M W Adler Physical dependence on morphine fads to develop during the hxbernatlng state Science 212 1527-1529 1981 2 Beckman, A L , C Llados-Eckman, T L Stanton and M W Adler Seasonal varmtlon of morphine physical dependence LtJe 5~t 30 147-153, 1982 3 Bdhngton, C J , T J Bartness A S Levtne, B H Herman and J E Morley Opmte feeding systems m guinea p~gs Fed Proc 43 1042, 1984 4 Bdhngton, C J , J E Morley, A S Lewne and G C Gerntsen Feeding systems in Chinese hamsters Am J Ph~ stol 247 R405-R411, 1984 5 Cooper, S J and S Turkish Food and water retake m the non-deprived p~geon after morphine or naloxone administration Neutopharmatoloe~ 20 1053-1058, 1981 6 Devlche, P and G Schepers Intracerebroventncular reJection of ostrich/3-endorphln to satmted pigeons reduces hyperphagm but not hyperdlpsla Pepttdes 5 691-694, 1984 7 Ghazarossmn V E , C Chavkm and A Goldsteln A specific radlolmmunoassay for the novel pephde, dynorphln Life S~t 27 75-86, 1980 8 Grandtson, L and A Gmdott~ St~mulatlon of food intake by musc~mol and beta endorphm Neurophatrna~olog,, 16 533536, 1977 9 King, M G , A J Kastm, R D Olsonand D H Coy Systemic admm~strahon of met-enkephahn, (D-ala~)-met-enkephahn, /3-endorphln, and (D-ala2)-/3-endorphln Effects on eating, drinkmg and acuwty measures m rats Pharmacol Bto~ hem Beha~ 11 407-411, 1979 10 Kromer, W Naltrexone influence on h~bernat~on E~pertentta 36 581-582, 1980 11 Levme, A S and J E Morley Pept~derglc control of insuhnreduced feeding PeptMes 2 261-264, 1981 12 Levme, A S and J E Morley Butorphanol tartrate reduces feeding m rats LtJe S~t 32 781-785, 1983

13 Levme, A S J E Morley D M Brown and B S Handwerger Extreme sens~hwty of dmbetlc mice to naloxonereduced suppression of food retake Phv~lol Beha~ 28 987-989 1982 14 Lowy M T , R P Malckel and G K W Ylm Naloxone reduction of stress-related feeding LtJe 5~ i 26 2113-2118, 1980 15 Lowy, M T and G K W Ylm Drinking, but not feeding, Js opiate-sensitive in hamsters LIte A~t 30 163%1644, 1982 16 Lo~y M T and G K W Ylm Stimulation of food retake following opiate agomsts m rats but not hamsters Pwt hophalma~olo~'~ (BeHm) 81 28-32, 1983 17 Margules D L Beta-endorphmandendoloxone Hormones of the autonomic nervous system for the conservation or expenditure of bodily resources and energy m anhctpatlon of famine or feast N e u t o ~ t Btobeha~ Re~ 3 155-162, 1979 18 Margules, D L , B Goldman and A Frock Hibernation An oplold-dependent state ) Brain Re~ Bull 4 721-724, 1979 19 Margules D L B Molsset M J Lewls, H ShlbuyaandC B Pert /3-Endorphm ts associated w~th overeating m geneUcally obese mice (ob/ob) and rats (fa/fa) 3 c w m e 202 988-991, 1978 20 McKay, L D N J Kenney N K Edens, R H Wdhamsand S C Woods lntracerebroventncular beta-endorphm increases food retake of rats LtJe Stt 29 142%1434, 1981 21 Messing, R B , B J Vasquez, V R Splehler, J L Martmee, J r , R A Jensen, H Rlgter and J L McGaush 3HDlhydromorphme binding m brain regions of young and aged rats LtJe S~t 26 921-927 1980 22 Morley J E , M K Elson, A S L e w n e a n d R B Shafer The effect of stress on the central nervous system concentrations of the oplold peptlde, dynorphm Pepttde~ 3 901-906, 1982 23 Morley J E and A S Levme Cortlcotrophm releasing factor grooming and mgestlve behavior LiJe Sct 31 145%1464, 1982 24 Morley J E and A S Levme Involvement of dynorphm and the kappa oplold receptor m feeding PeptMe~ 4 797-800, 1983

OPIOID MODULATION

IN THE GROUND SQUIRREL

25 Morley, J E and A S Levme The pharmacology of eating behavior Annu Rev Pharmacol Tortcol 25 127-146, 1985 26 Morley, J E , A S Levlne, M Grace and J Knelp An mvesttgatlon of the role of kappa opmte receptor agonlsts m the ruination of feeding Ltfe Sct 31. 2617-2626, 1982 27 Morley. J E , A S Levme, G K Y l m a n d M T Lowy Oplold modulation of appetite Neurosct Btobehav Rev 7 281-305, 1983 28 Mrosovsky, N Lipid programmes and hfe strategies in hibernators Am Zoo! 16 685-697, 1976

9

29 Nlzlelskl, S E , J E Morley, T J Bartness, U S Seal and A S Levme Effects of mampulatlons of glucoregulatlon on feeding in the ground squirrel Phystol Behav 36 53-58, 1985 30 Nlzlelskl, S E , J E Morley, B A Gosnell, U S Sealand A S Levme Opio~d modulation of ingestive behawors in woodchucks and racoons Phystol Behav 34 171-176, 1985 31 Vaupel, D B and E C Morton Anorexia and hyperphagm produced by five pharmacologic classes of hallucinogens Pharmacol Btochem Beha~ 17 539-545. 1982