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Naloxone suppresses intake of highly preferred saccharin solutions in food deprived and sated rats
Life Sciences, Vol. 33, pp. 1909-1914 Printed in the U.S.A.
Pergamon Press
NALOXONE SUPPRESSES INTAKE OF HIGHLY PREFERRED SACCHARIN SOLUTIONS IN FOOD DEPRIVED AND SATED RATS Wesley C. Lynch and Leslie Libby Department of Psychology, Montana State University Bozeman, Montana 59717 (Received in final form August 17, 1983) Summary In repeated tests naloxone (1 mg/kg, SC) suppressed intake of a narrow range of highly preferred saccharin concentrations (0.1 and 1.0%) in nondeprived male rats but a wider range of concentrations (.OOl - 1.0%) following 10 hr. food deprivation. In sated rats a low dose of morphine (0.1 mg/kg, SC) had no effect on intake of low concentrations of saccharin but significantly facilitated intake of the highest (10%) and least preferred concentration. These data support the hypothesis that endogenous opioids can modulate the affective quality of gustatory stimuli. Opiate antagonists inhibit food and water intake induced by deprivation (l-8), by acute physiological challenge other than deprivation (5, 9, 10) and, in certain cases, under neutral, ad libitum conditions (5, 11, 12, 13, 14). Opiate agonists, including certairezus opioids, facilitate intake. For instance, systemic morphine and levorphanol enhance intake of both food and water in mildly deprived (3) and sated (5) rats, while the (-)-opiate agonist dextrorphan is ineffective (5). Similarly, morphine infused directly into the ventromedial hypothalamus (15) and $-endorphin infused into the paraventricular nucleus (9) enhance food intake. Oral palatability factors appear to influence the suppressive effectiveness of opiate antagonists. Apfelbaum and Mandenoff (11) reported naltrexone suppressed intake of a highly palatable diet in rats (cakes, noodles, lard, chocolate) but not a normal chow diet. Levine, et al. (8) showed that lower doses of naloxone (0.5 - 1.0 mg/kg) are required to suppress intake of sapid solutions of saccharin (0.2%), NaCl (0.8%), sucrose (2%) and HCl (0.1 M), than to suppress water intake (5 mg/kg). Previously, LeMagnen,et al. (12) reported that naloxone (1 mg/kg) abolished preference for sweet solutions of saccharin and glucose and suppressed intake of bitter quinine and saccharin solutions made aversive by conditioned taste aversion (CTA) training. Rockwood, et al. (16) also implicated oral factors in opiate effects on intake by demonstrating that naloxone reduces sham water intake in rats with open gastric fistulas. The present study examined the effects of naloxone (NAL) and morphine (MOR) on the classic 2-bottle taste preference/aversion (P/A) curve (17). Previous work suggests that opiate antagonists may depress intake by decreasing the palatability of highly preferred tastes (8). In particular, the work of LeMagnen, et al. (12) led to the suggestion that NAL decreases preference for sweets and enhances aversion to bitter (quinine) and to sweets made aversive by CTA. Levine et al. (8) on the basis of their work suggested that, "opiate
0024-3205/83 $3.00 + .OO Copyright (c) 1983 Pergamon Press Ltd.
1910
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
blockade alters taste perception, perhaps by diminishing the perception of sweet and salt and increasing perception of sour." (p.25). Such results imply either a downward or leftward shift in the classic P/A curve. Methods Subjects. Twenty adult male Sprague-Dawley albino rats, were repeatedly tested over 7 weeks. Animals were on a 14 hr/lO hr light/dark cycle with lights on daily at10 am. Regular testing was done Monday through Friday 8-11 pm. Prior to the start of regular tests each rat was given a single 24 hr access to saccharin (O.l%), in addition to normally available food and water. Each session consisted of placing 2 calibrated (100 ml) bottles on each animal's home cage for 60 min. One bottle always contained distilled water, the other contained 1 of 5 solutions of sodium saccharin (.OOl, .Ol, 0.1, 1.0 or 10.0%). All rats received each concentration once per week in counterbalanced order. Drug treatments varied from week to week. Weekly protocols were as follows: All animals had free access to food and water throughout the first 4 weeks of testing. During weeks 1 and 2 each test session was preceded by a 1 ml/kg injection 0.9% NaCl (SC) given 15 min before water bottles were presented. During week 3 each test was preceded (15 min) by a 1 mg/kg injection of naloxone-HCl (SC) and during week 4 (30 min) by a 0.1 mg/kg injection of morphine sulfate (SC). This low morphine dose was arbitrarily chosen in an attempt to stimulate u-receptors without producing untoward motor effects. Throughout week 5 all animals were adapted to food deprivation. During this and subsequent weeks food was available for 1 hr daily, 10 hours before scheduled testing. Tap water was freely available at all times. Animals were again given taste preference tests on weeks 6 and 7, while remaining on this deprivation schedule. During week 6 they again received 1 mg/kg (SC) injections of 0.9% NaCl (SAL) and during week 7, 1.0 mg/kg (SC) injections of naloxone (NAL), both injections given 15 min before testing began. Results All data were analyzed by paired t-tests. Week 2 (nondeprived, SAL) provided the comparative baseline for weeks 3 (NAL) and 4 (MOR). Week 6 (deprived, SAL) provided the baseline for week 7 (NAL). Figure 1 shows the results for -ad lib weeks 2 (SAL), 3 (NAL) and 4 (MOR). As can be seen, naloxone dramatically reduced intake of two of the most preferred concentrations: 0.1% (t = 6.67, df = 19, p < .OOl) and 1.0% (t = 3.15, df = 19, p < .005) but had no significant effect on any saccharin concentration above or below these. On the other hand, MOR at the low dose used (0.1 mg/kg) had a mildly facilitative effect on intake of only the highest saccharin concentration: 10% (t = 2.27, df = 19, p < .05). Figure 2 shows the effect of NAL on saccharin intake following food deprivation. Again, NAL strongly suppressed the intake of the 0.1% (t = 4.45, df = 17, p < .OOl) and 1.0% (t = 5.70, df = 19, p < .OOl) concentrations. Under these deprivation conditions, however, it significantly suppressed intake of the 2 lower concentrations as well: .Ol% (t = 6.43, df = 19, p < .OOl) and .OOl% (t = 2.21, df = 19, p < .025).
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
1911
14
o---MOR 12
-SAL .--
NAL
10 = E wa 2 z -6 % =4 w 0’ 2
0
I
0
I
I
,001
.Ol 90
I
0.1
I
I
1.0
10.0
SACCHARIN
Fig. 1 One hour intake of saccharin solutions in nondeprived male rats following each of 3 treatments: MOR - morphine sulfate (0.1 mg/kg, SC, 30 min before testing), SAL - 0.9% NaCl (1 ml/kg, SC, 15 min before testing) and NAI. - naloxone - HCl (1.0 mg/kg, SC, 15 min before testing). Numerals indicate significant differences between drug (MOR or NAL) and SAL according to paired t-tests (1 = p < .05, 2 = p < .005, 3 = p < .OOl>. Discussion These results suggest that oral palatability factors play a significant role in the modulation of opiate effects on fluid intake. It seems unlikely that naloxone's suppression of intake was due to a general inhibition of motor performance or to illness since it only affected intake of selected, preferred concentrations. Following mild food deprivation, naloxone suppressed a broader range of concentrations but even in this case naloxone did not suppress intake of water or of the highest (10%) saccharin concentration. Thus, it appears that naloxone's strongest effect in both cases is limited to the most palatable midrange of taste stimuli. In sated rats intake of the most preferred 0.1% solution was suppressed in 19 of 20 animals (95%) who showed a mean inhibition of intake of 50.4%. At the 1.0% concentration intake was suppressed in only 12 animals (60%) but in those 12 there was a 63.6% suppression. This suggests that naloxone is highly effective at this saccharin concentration in certain animals but ineffectivesin others. The source of such individual differences is currently unknown.
1912
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
12
10
18
16
z
14
2 ;
12
5
10
0 I w
8
5 6
4
2 01
I
0
I.
L
.OOl
.Ol o/o
1
0.1
I
I
1.0
10.0
SACCHARIN
Fig. 2 One hour intake of saccharin solutions in 10 hr food deprived male rats following 2 treatments: SAL - 0.9% NaCl (1 ml/kg, SC, 15 min before testing) and NAL - naloxone - HCl (1.0 mg/kg, SC, 15 min before testing). Numerals indicate significant differences between SAL and NAL according to paired t-tests (1 = p < .OS, 3 = p < .OOl). The effect of morphine on intake of the 10% solution of saccharin in sated rats may be related to the aversive ("bitter") quality of this high concentration. As Figure 1 shows, control (SAL) intake of this concentration was less than intake of water. Since in humans this concentration has a strong bitter after-taste, it seems possible that a similar aversive quality to this concentration may account for this depressed intake in saline injected rats. Following MOR injection, however, rats consumed nearly as much of the 10% solution as they did water and significantly more than they had under control conditions. This finding supports the idea that opiate receptor stimulation may either enhance the sweet or depress the bitter quality of this concentration. The latter interpretation seems more plausible since MOR did not facilitate intake of lower , primarily sweet, concentrations. In previous work LeMagnen,
Vol. 33, No. 19, 1983
Naloxone and Taste Preference
1913
et al. (12) reported that naloxone inhibited intake of bitter quinine solutions and intake of sweet solutions made aversive by CTA. Similarly, Levine, et al. (8) reported a suppression of intake of a sour 0.1 M HCl solution and a small (but insignificant) suppressive effect of NAL on quinine intake. These results suggested that opiate antagonists might enhance the aversive properties of sour and bitter tastes. Our results with morphine, although very tentative, suggest that opiate agonists may attenuate the aversive (bitter) properties of gustatory stimuli. It is clear, however, that further research is needed to verify this possibility. When deprived of food, rats increased their intake of a wider range of saccharin concentrations. Likewise, following deprivation, naloxone suppressed intake of a wider range of concentrations. These results are consistent with the view that deprivation enhances preference for normally less preferred tastes and that opiate receptor blockade reverses this effect. It appears that naloxone produced a greater percentage reduction of intake of the most preferred (0.1%) concentration of saccharin under nondeprived than deprived conditions. This seems to suggest that deprivation and opiate receptor blockade act in opposite directions. On the other hand, deprivation enhanced the effectiveness of naloxone at lower saccharin concentrations, suggesting that taste preference rather than hunger is modulated by naloxone. Thus, whether naloxone would be more or less effective in suppressing intake of standard rat chow in deprived (versus sated) animals would seem to depend on food palatibility. Food intake was not monitored in the present experiments. We have observed that nondeprived rats rarely drink large quantities of even the most highly preferred saccharin concentration on their first exposure to it but must instead gradually "acquire" a taste for it. This suggests that endogenous opioids may be released in central taste pathways (18) by the anticipation of repeated tests and, thereafter, may mediate enhanced acceptance of sweets. Opiate blockade might suppress sweet intake by blocking opiate receptors involved in such gustatory learning. In support of this notion it has been shown that agonists, including the endogenous opiate $-endorphin injected both peripherally (3, 5, 19) and centrally into the paraventricular hypothalamic "feeding" area (9) and morphine injected into the ventromedial hypothalamus (15), stimulate food intake. Moreover, opiate receptors have been reported to exist in central taste pathways including the nucleus of the solitary tract, the thalamic taste are and extensively throughout the hypothalamus (20). Further, morphine has been shown to inhibit gustatory activity in the pontine taste area (21) and this effect is reversed by naloxone. Morley and Levine (22) showed that the endogenous K-opiate receptor agonist dynorphin - (1-13) induces feeding in sated rats and subsequently they (23) and others (24) suggested that the r-receptor may be a selective initiator of feeding. While the present results do not reflect directly on the involvement of any specific receptor subtype, they do suggest that certain endogenous opiates may normally modulate the affective quality of gustatory events. Acknowledgements We wish to express our thanks to Endo Laboratories for providing Naloxone. This work was supported in part by the MONTS-NSF project ISP-8011449.
1914
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
References 1.
2. 3. 4. 5. 6. 7.
8. 9. IO.
11. -12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
H. FRENK and G. H. ROGERS, Behav. Neural Biol. 26 23-40 (1979). H. FRENK and J. B. ROSEN, Pharmac. Biochem. Behz. 11 387-390 (1979). J. E. JALOWIEC, J. PANKSEPP, A. J. ZOLOVICK, N. NA.JE and B. H. HERMAN, Pharmac. Biochem. Behav. 15 477-484 (1981). M. T. LOWY and G. K. W. Yz, Neuropharmac. 20 883-886 (1981). M. T. LOWY, C. STARKEY and G. K. W. YIM, Phzac. Biochem. Behav. -15 591-596 (1981). P. S. MCCARTHY, P. W. DETTMAR, A. G. LYNN and D. J. SANGER, Neuropharmac. 20 1347-1349 (1981). CM. SIVIY, F. BERMUDEZ-RATTONI, G. A. ROCKWOOD, C. M. DARGIE and L. D. REID, Pharmac. Biochem. Behav. 15 257-262 (1981). A. S. LEVINE, S. S. MURRAY, J. %EIP, M. GRACE and J. E. MORLEY, Physiol. Behav. 28 23-25 (1982). S. F. LEBOWITZ and L. HOR, Peptides 2 421-428 (1982). N. ROWLAND and T. J. BARTNESS, Pharmac. Biochem. Behav. -16 1001-1013 (1982). M. APFELBAUM and A. MANDENOFF, Pharmac. Biochem. Behav. 15 89-91 (1981). J. LEMAGNEN, P. MARFAING-JALLAT, D. MICELI and M. DEVOS,?harmac. Biochem. Behav. 12 729-733 (1980). I. M. LEG, J. C. STRAHLENDORF, H. K. STRAHLENDORF, L. 0. LUTHERER and C. D. BARNES, Pharmac. Biochem. Behav. 16 909-913 (1982). A. MANDENOFF, F. FUMERON, M. APFELBAUM and D. L. MARGULES, Science -215 1536-1538 (1982). F. S. TEPPERMAN, M. HIRST and C. W. GOWDEY, Pharmac. Biochem. Behav. -15 555-558 (1981). G. A. ROCKWOOD, S. M. SIVIY and L. D. REID, Pharmac. Biochem. Behav. -15 319-321 (1981). C. PFAFFMANN, In J. T. Tapp (ed.) Reinforcement and Behavior, pp. 215-241, Academic Press, New York (1969). R. NORGEN, In .I.LEMAGNEN, and P. MACLEOD (eds.), Olfaction and Taste VI pp. 225-232, Information Retrieval, London (1977). S. GRANDISON and A. GUIDOTTI, Neuropharmac. 16 533-536 (1977). M. HERKENHAM and C. B. PERT, J. Neurosci. 2=29-1149 (1982). G. HERMANN and D. NOVIN, Brain Res. Bull. 5(S4) 169-173 (1980). J. E. MORLEY and A. S. LEVINE, Life Sci. 29 1901-1903 (1982). J. E. MORLEY, A. S. LEVINE, M. GRACE and TKNIEP. Life Sci. 2, 26172626 (1982). K. W. LOCKE, D. R. BROWN and S. G. HOLTMAN, Phannac. Biochem. Behav. -17 1275-1279 (1982).
Pergamon Press
NALOXONE SUPPRESSES INTAKE OF HIGHLY PREFERRED SACCHARIN SOLUTIONS IN FOOD DEPRIVED AND SATED RATS Wesley C. Lynch and Leslie Libby Department of Psychology, Montana State University Bozeman, Montana 59717 (Received in final form August 17, 1983) Summary In repeated tests naloxone (1 mg/kg, SC) suppressed intake of a narrow range of highly preferred saccharin concentrations (0.1 and 1.0%) in nondeprived male rats but a wider range of concentrations (.OOl - 1.0%) following 10 hr. food deprivation. In sated rats a low dose of morphine (0.1 mg/kg, SC) had no effect on intake of low concentrations of saccharin but significantly facilitated intake of the highest (10%) and least preferred concentration. These data support the hypothesis that endogenous opioids can modulate the affective quality of gustatory stimuli. Opiate antagonists inhibit food and water intake induced by deprivation (l-8), by acute physiological challenge other than deprivation (5, 9, 10) and, in certain cases, under neutral, ad libitum conditions (5, 11, 12, 13, 14). Opiate agonists, including certairezus opioids, facilitate intake. For instance, systemic morphine and levorphanol enhance intake of both food and water in mildly deprived (3) and sated (5) rats, while the (-)-opiate agonist dextrorphan is ineffective (5). Similarly, morphine infused directly into the ventromedial hypothalamus (15) and $-endorphin infused into the paraventricular nucleus (9) enhance food intake. Oral palatability factors appear to influence the suppressive effectiveness of opiate antagonists. Apfelbaum and Mandenoff (11) reported naltrexone suppressed intake of a highly palatable diet in rats (cakes, noodles, lard, chocolate) but not a normal chow diet. Levine, et al. (8) showed that lower doses of naloxone (0.5 - 1.0 mg/kg) are required to suppress intake of sapid solutions of saccharin (0.2%), NaCl (0.8%), sucrose (2%) and HCl (0.1 M), than to suppress water intake (5 mg/kg). Previously, LeMagnen,et al. (12) reported that naloxone (1 mg/kg) abolished preference for sweet solutions of saccharin and glucose and suppressed intake of bitter quinine and saccharin solutions made aversive by conditioned taste aversion (CTA) training. Rockwood, et al. (16) also implicated oral factors in opiate effects on intake by demonstrating that naloxone reduces sham water intake in rats with open gastric fistulas. The present study examined the effects of naloxone (NAL) and morphine (MOR) on the classic 2-bottle taste preference/aversion (P/A) curve (17). Previous work suggests that opiate antagonists may depress intake by decreasing the palatability of highly preferred tastes (8). In particular, the work of LeMagnen, et al. (12) led to the suggestion that NAL decreases preference for sweets and enhances aversion to bitter (quinine) and to sweets made aversive by CTA. Levine et al. (8) on the basis of their work suggested that, "opiate
0024-3205/83 $3.00 + .OO Copyright (c) 1983 Pergamon Press Ltd.
1910
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
blockade alters taste perception, perhaps by diminishing the perception of sweet and salt and increasing perception of sour." (p.25). Such results imply either a downward or leftward shift in the classic P/A curve. Methods Subjects. Twenty adult male Sprague-Dawley albino rats, were repeatedly tested over 7 weeks. Animals were on a 14 hr/lO hr light/dark cycle with lights on daily at10 am. Regular testing was done Monday through Friday 8-11 pm. Prior to the start of regular tests each rat was given a single 24 hr access to saccharin (O.l%), in addition to normally available food and water. Each session consisted of placing 2 calibrated (100 ml) bottles on each animal's home cage for 60 min. One bottle always contained distilled water, the other contained 1 of 5 solutions of sodium saccharin (.OOl, .Ol, 0.1, 1.0 or 10.0%). All rats received each concentration once per week in counterbalanced order. Drug treatments varied from week to week. Weekly protocols were as follows: All animals had free access to food and water throughout the first 4 weeks of testing. During weeks 1 and 2 each test session was preceded by a 1 ml/kg injection 0.9% NaCl (SC) given 15 min before water bottles were presented. During week 3 each test was preceded (15 min) by a 1 mg/kg injection of naloxone-HCl (SC) and during week 4 (30 min) by a 0.1 mg/kg injection of morphine sulfate (SC). This low morphine dose was arbitrarily chosen in an attempt to stimulate u-receptors without producing untoward motor effects. Throughout week 5 all animals were adapted to food deprivation. During this and subsequent weeks food was available for 1 hr daily, 10 hours before scheduled testing. Tap water was freely available at all times. Animals were again given taste preference tests on weeks 6 and 7, while remaining on this deprivation schedule. During week 6 they again received 1 mg/kg (SC) injections of 0.9% NaCl (SAL) and during week 7, 1.0 mg/kg (SC) injections of naloxone (NAL), both injections given 15 min before testing began. Results All data were analyzed by paired t-tests. Week 2 (nondeprived, SAL) provided the comparative baseline for weeks 3 (NAL) and 4 (MOR). Week 6 (deprived, SAL) provided the baseline for week 7 (NAL). Figure 1 shows the results for -ad lib weeks 2 (SAL), 3 (NAL) and 4 (MOR). As can be seen, naloxone dramatically reduced intake of two of the most preferred concentrations: 0.1% (t = 6.67, df = 19, p < .OOl) and 1.0% (t = 3.15, df = 19, p < .005) but had no significant effect on any saccharin concentration above or below these. On the other hand, MOR at the low dose used (0.1 mg/kg) had a mildly facilitative effect on intake of only the highest saccharin concentration: 10% (t = 2.27, df = 19, p < .05). Figure 2 shows the effect of NAL on saccharin intake following food deprivation. Again, NAL strongly suppressed the intake of the 0.1% (t = 4.45, df = 17, p < .OOl) and 1.0% (t = 5.70, df = 19, p < .OOl) concentrations. Under these deprivation conditions, however, it significantly suppressed intake of the 2 lower concentrations as well: .Ol% (t = 6.43, df = 19, p < .OOl) and .OOl% (t = 2.21, df = 19, p < .025).
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
1911
14
o---MOR 12
-SAL .--
NAL
10 = E wa 2 z -6 % =4 w 0’ 2
0
I
0
I
I
,001
.Ol 90
I
0.1
I
I
1.0
10.0
SACCHARIN
Fig. 1 One hour intake of saccharin solutions in nondeprived male rats following each of 3 treatments: MOR - morphine sulfate (0.1 mg/kg, SC, 30 min before testing), SAL - 0.9% NaCl (1 ml/kg, SC, 15 min before testing) and NAI. - naloxone - HCl (1.0 mg/kg, SC, 15 min before testing). Numerals indicate significant differences between drug (MOR or NAL) and SAL according to paired t-tests (1 = p < .05, 2 = p < .005, 3 = p < .OOl>. Discussion These results suggest that oral palatability factors play a significant role in the modulation of opiate effects on fluid intake. It seems unlikely that naloxone's suppression of intake was due to a general inhibition of motor performance or to illness since it only affected intake of selected, preferred concentrations. Following mild food deprivation, naloxone suppressed a broader range of concentrations but even in this case naloxone did not suppress intake of water or of the highest (10%) saccharin concentration. Thus, it appears that naloxone's strongest effect in both cases is limited to the most palatable midrange of taste stimuli. In sated rats intake of the most preferred 0.1% solution was suppressed in 19 of 20 animals (95%) who showed a mean inhibition of intake of 50.4%. At the 1.0% concentration intake was suppressed in only 12 animals (60%) but in those 12 there was a 63.6% suppression. This suggests that naloxone is highly effective at this saccharin concentration in certain animals but ineffectivesin others. The source of such individual differences is currently unknown.
1912
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
12
10
18
16
z
14
2 ;
12
5
10
0 I w
8
5 6
4
2 01
I
0
I.
L
.OOl
.Ol o/o
1
0.1
I
I
1.0
10.0
SACCHARIN
Fig. 2 One hour intake of saccharin solutions in 10 hr food deprived male rats following 2 treatments: SAL - 0.9% NaCl (1 ml/kg, SC, 15 min before testing) and NAL - naloxone - HCl (1.0 mg/kg, SC, 15 min before testing). Numerals indicate significant differences between SAL and NAL according to paired t-tests (1 = p < .OS, 3 = p < .OOl). The effect of morphine on intake of the 10% solution of saccharin in sated rats may be related to the aversive ("bitter") quality of this high concentration. As Figure 1 shows, control (SAL) intake of this concentration was less than intake of water. Since in humans this concentration has a strong bitter after-taste, it seems possible that a similar aversive quality to this concentration may account for this depressed intake in saline injected rats. Following MOR injection, however, rats consumed nearly as much of the 10% solution as they did water and significantly more than they had under control conditions. This finding supports the idea that opiate receptor stimulation may either enhance the sweet or depress the bitter quality of this concentration. The latter interpretation seems more plausible since MOR did not facilitate intake of lower , primarily sweet, concentrations. In previous work LeMagnen,
Vol. 33, No. 19, 1983
Naloxone and Taste Preference
1913
et al. (12) reported that naloxone inhibited intake of bitter quinine solutions and intake of sweet solutions made aversive by CTA. Similarly, Levine, et al. (8) reported a suppression of intake of a sour 0.1 M HCl solution and a small (but insignificant) suppressive effect of NAL on quinine intake. These results suggested that opiate antagonists might enhance the aversive properties of sour and bitter tastes. Our results with morphine, although very tentative, suggest that opiate agonists may attenuate the aversive (bitter) properties of gustatory stimuli. It is clear, however, that further research is needed to verify this possibility. When deprived of food, rats increased their intake of a wider range of saccharin concentrations. Likewise, following deprivation, naloxone suppressed intake of a wider range of concentrations. These results are consistent with the view that deprivation enhances preference for normally less preferred tastes and that opiate receptor blockade reverses this effect. It appears that naloxone produced a greater percentage reduction of intake of the most preferred (0.1%) concentration of saccharin under nondeprived than deprived conditions. This seems to suggest that deprivation and opiate receptor blockade act in opposite directions. On the other hand, deprivation enhanced the effectiveness of naloxone at lower saccharin concentrations, suggesting that taste preference rather than hunger is modulated by naloxone. Thus, whether naloxone would be more or less effective in suppressing intake of standard rat chow in deprived (versus sated) animals would seem to depend on food palatibility. Food intake was not monitored in the present experiments. We have observed that nondeprived rats rarely drink large quantities of even the most highly preferred saccharin concentration on their first exposure to it but must instead gradually "acquire" a taste for it. This suggests that endogenous opioids may be released in central taste pathways (18) by the anticipation of repeated tests and, thereafter, may mediate enhanced acceptance of sweets. Opiate blockade might suppress sweet intake by blocking opiate receptors involved in such gustatory learning. In support of this notion it has been shown that agonists, including the endogenous opiate $-endorphin injected both peripherally (3, 5, 19) and centrally into the paraventricular hypothalamic "feeding" area (9) and morphine injected into the ventromedial hypothalamus (15), stimulate food intake. Moreover, opiate receptors have been reported to exist in central taste pathways including the nucleus of the solitary tract, the thalamic taste are and extensively throughout the hypothalamus (20). Further, morphine has been shown to inhibit gustatory activity in the pontine taste area (21) and this effect is reversed by naloxone. Morley and Levine (22) showed that the endogenous K-opiate receptor agonist dynorphin - (1-13) induces feeding in sated rats and subsequently they (23) and others (24) suggested that the r-receptor may be a selective initiator of feeding. While the present results do not reflect directly on the involvement of any specific receptor subtype, they do suggest that certain endogenous opiates may normally modulate the affective quality of gustatory events. Acknowledgements We wish to express our thanks to Endo Laboratories for providing Naloxone. This work was supported in part by the MONTS-NSF project ISP-8011449.
1914
Naloxone and Taste Preference
Vol. 33, No. 19, 1983
References 1.
2. 3. 4. 5. 6. 7.
8. 9. IO.
11. -12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.
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