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Effect of exogenous arginine vasopressin on rectal temperature in the Albino rat
HORMONES
AND
BEHAVIOR
15,
226-231 (1981)
BRIEF REPORT Effect of Exogenous Arginine Vasopressin Temperature in the Albino Rat A. F. CRINE,*~‘*~ *Laboratory
of
S. BREDART,*
on Rectal
AND J. J. LEGROS~
Experimental Psychology and TNeuroendocrinology University of Likge. B4020 Ligge, Belgium
Section,
One subcutaneous injection of arginine vasopressin (2.0 I.U./kg.) in SpragueDawley male rats caused a decrease in rectal temperature. A slight fall was also noted in the placebo group but there were statistically significant differences. This result was discussed in terms of modification of emotional processes.
Since the early works on the effect of posterior hypophysectomy on acquired behavior (de Wied, 1965), vasopressin has been tested in behavioral situations such as active and passive avoidance conditioning (de Wied, 1971; Ader and de Wied, 1972; Bohus, Ader, and de Wied, 1972; de Wied, 1976a), appetitive maze conditioning (Bohus, 1977), and imprinting (Martin and van Wimersma Greidanus, 1979). Generally, vasopressin and its analogs induced an increased resistance to extinction, more rapid acquisition, and improved retention performance in avoidance and appetitive tests. These effects have been interpreted in terms of vasopressin effects on memory consolidation and retrieval of information (de Wied, 1976b; van Ree, Bohus, Versteeg, and de Wied, 1978; de Wied, 1979; de Wied and Bohus, 1979). We have measured the effects of systemic administration of arginine vasopressin (AVP) on body temperature in the rat. This type of investigation is not new since peripheral injections of lysine vasopressin have already been shown induce a fall in rectal temperature in the rat (Okuno, Yamamoto, and Itoh, 1965). More recently, Kasting, Veale, and Cooper (1980) have demonstrated a hypothermic effect of AVP after intraventricular administration. Moreover, intracerebral injections of AVP have been reported to reduce fever in sheep (Cooper, Kasting, Lederis, and ’ Aspirant FNRS. 2 To whom requests for reprints should be sent at: Laboratory of Experimental ogy, University of Liege, Blvd. de la Constitution, 32 Liege, Belgium. 226 0018-506X/81/020226-06$01.00/0 Copyright All rights
@ 1981 by Academic Press. Inc. of reproduction in any form reserved.
Psychol-
BRIEF
REPORT
227
Veale, 1979), and the increase in body temperature resulting from high environmental temperatures is related to an increase in plasma AVP in pigs (Forsling, Ingram, and Stanier, 1976). In addition, stimulation such as the increase in temperature at the beginning of spring induces a massive secretion of vasopressin in hibernants (Legait, Burlet, and Marchetti, 1970). Conversely, secretion of endogenous vasopressin induced by hypertonicity of circulating fluid can cause a temperature decrease (Gkuno et al., 1965). However, exogenously administered vasopressin does not suppress the increase of body temperature caused by heat exposure (Okuno ef al., 1965). Finally, in contrast to the finding of Kasting et al. (1980), Lipton and Glyn (1980) reported that intraventricular injections of AVP produced hyperthermia in the rabbit. Therefore, the role of vasopressin in the modulation of body temperature is not clear and this research was aimed at clarifying the relationship between vasopressin and body temperature. Methods. Subjects. Twenty-two male Sprague-Dawley rats (Animalabo, Brussels, Belgium) weighing 340-380 g at the beginning of the experiments were housed in groups. Food and water were available ad lib and the 1ight:dark cycle was IO:14 hr. Apparatus. A rectal thermometer (DU-3 ELLAB Copenhagen, Denmark) was used in this experiment. Its two probes allow the simultaneous measurement of temperatures in two animals. The apparatus in which each rat was maintained during temperature measurements is prismatic in shape, made of transparent Plexiglas, and has air-conducting holes on each side. The ambient room temperature was 26 2 1°C and experimental room was not soundproof. Procedure. Each rat was removed from its home cage, placed directly in the immobility apparatus, and the rectal thermometer was inserted. During the following 20 min, the animals were not subjected to any other treatment. This period permitted habituation to the apparatus. At the end of this period, the temperature was taken and the treatment given. The experimental group (n = 12) was injected subcutaneously with arginine vasopressin (SANDOZ) at a dose of 2.0 IU/kg in 5.0 ml saline. The placebo group (n = 10) was injected subcutaneously with NaClO.9%, 5.0 ml/kg, under the same conditions. Immediately after the injection, the rat was placed again in the immobility apparatus and the rectal probe reinserted. The temperature was measured for the second time as soon as the probe was reinserted; for the third time 10 min later, and then every 5 min until 90 min had passed. All measures were taken between 2 and 6 PM. Results. The change in rectal temperature over time for both experimental and control rats is presented in Fig. 1. The statistical analysis (Student’s test) shows a decrease in temperature in both groups. This decrease became significantly different from base line after 30 min in the
228
BRIEF
REPORT
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BRIEF
REPORT
229
group that received AVP (t(22) = -2.69; p < .02), and in the placebo group after 70 min (t(18) = -2.21;~ < .05). Furthermore, the decrease in temperature was significantly larger in the experimental group than in the placebo group between the 35th and the 55th min (t(20) = -2.65, -2.76, -2.26, -2.22, -2.33, respectively;p < .02 for the former twot’s andp < .05 for the latter three t’s). Discussion. An injection of 2.0 W/kg of arginine vasopressin induced a significant decrease in rectal temperature. Although a slight fall in rectal temperature was also seen in the placebo group, there were statistically significant differences between the two groups. In 1965, Okuno er al. reported similar effects after peripheral injection of lysine vasopressin. In 1980, Kasting et al. also noted a decrease in rectal temperature after intraventricular injections of AVP. However, contrary to our results (see Fig. 1) the rectal temperature of animals injected with vasopressin returned to base line after 90 and 40 min, respectively, and there was no decrease in rectal temperature in the placebo group. These two inconsistencies may be important in a further analysis of vasopressin as a hypothermic agent. It is possible that the apparatus used to immobilize the animals during the experiment is aversive and consequently can induce a rise in temperature as hyperthermic reaction can be a somatic response to aversive situations (Delini-Stula, 1970). The effect of vasopressin would not be a pure physiological effect, but rather, vasopressin may play the role of an adaptor to the aversive situation. In this case, vasopressin may decrease the aversity (= emotivity! ?) level. However, a peripheral interpretation for the modulation of body temperature by vasopressin was offered by Itoh, Tsukada, Okuno, and Yoshinari (1966), Itoh, Tsukada, and Omoe (1967), and Moriya and Itoh (1969). They hypothesized that the decrease in temperature results from a reduction in metabolic rate caused by a lowering of the plasma-free fatty acid level. In contrast, Cooper et al. (1979) found that the septal region is an important substratum for the vasopressin-induced decrease in fever. It is not yet clear whether the vasopressin effect on fever and on normal body,temperature is mediated by similar mechanisms. If such is the case, the interpretation offered here may be especially valid when it is recalled that septal region is a brain region that has been implicated in emotion (Papez, 1937). However, as long as reports of the effect of vasopressin on body temperature are conflicting (see results obtained by Kasting et al. (1980) vs Lipton and Glyn (1980)), this interpretation will remain very limited. Therefore, it is necessary to systematically reanalyze the effect of vasopressin and its analogs in several species, with wide range of doses, using both peripheral and central routes of administration, and variations in the ambient temperature before firm conclusions can be drawn.
230
BRIEF
REPORT
ACKNOWLEDGMENTS This
study
was supported
by Grant
3.4507.79
from
the Belgian
FRSM.
REFERENCES Ader,
R., and de Wied, D. (1972). Effects of lysine vasopressin on passive avoidance learning. Psychon. Sri. 29, 46-48. Bohus, B., Ader, R., and de Wied, D. (1972). Effects of vasopressin on active and passive avoidance behavior. Horm. Behav. 3, 191-197. Bohus, B. (1977). Effect of desglycinamide-lysine vasopressin (DG-LVP) on sexually motivated T-maze behavior in the male rat. Horm. Behav. 8, 52-61. Cooper, K. E., Kasting, N. W., Lederis, K., and Veale, W. L. (1979). Evidence supporting a role for endogenous vasopressin in natural suppression of fever in the sheep. J. Physiol. 295, 33-45. Delini-Stula, A. (1970). The development and the extinction of hyperthermia induced by conditioned avoidance behavior in rats. J. Exp. Anal. Behav. 14, 213-218. de Wied, D. (1965). The influence of the posterior and intermediate lobe of the pituitary and pituitary peptides on the maintenance of a conditioned avoidance response in rats. fnt. J. Neuropharmacol. 4, 157-167. de Wied, D. (1971). Long term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature (London) 232, 58-60. de Wied, D. (1976). Behavioral effects of intraventricularly administered vasopressin and vasopressin fragments. Lije Sci. 19, 685-690. (a) de Wied, D. (1976). Hormonal influences on motivation, learning and memory processes. Hosp. Pruct. 11, 123-131. (b) de Wied, D. (1979). Pituitary neuropeptides and behavior. In K. Juxe, T. Hokfelt, and R. Luft (Eds.), Central Regulation of the Endocrine System, pp. 297-314. Plenum, New York. de Wied, D., and Bohus, B. (1979). Modulation of memory processes by neuropeptides of hypothalamic-neurohypophyseal origin. In M. A. B. Brazier (Ed.), Brain Mechanisms in Memory and Learning: From the Single Neuron to Man, pp. 139-149. Raven Press. New York. Forsling, M. L., Ingram, D. M.. and Stanier, M. W. (1976). Effects of various ambient temperatures and of heating and cooling the hypothalamus and cervical spinal cord on antidiuretic hormone and urinary osmolahty. J. Physiol. 257, 673-686. Itoh, S., Tsukada, M., Okuno, A., and Yoshinari, T. (1966). Effects of vasopressin on the plasma concentration of free fatty acids and in vitro oxygen consumption of tissues of the rat. Japan. J. Physiol. 16, 23-30. Itoh, S., Tsukada, M., and Omoe, K. (1967). Effect of vasopressin on plasma lipids in the rat. Japan. J. Physiol. 17, 667-677. Kasting, N. W., Veale, W. L., and Cooper, K. E. (1980). Convulsive and hypothermic effects of vasopressin in the brain of the rat. Canad. J. Physiol. Pharmacol. 58, 316-319. Legait, E., Burlet, C., and Marchetti, J. (1970). Contribution a I’etude du systeme hypothalamo-neurohypophysaire au tours de I’hibernation. In W. Borgmann and B. Scharrer (Eds.),Aspecfs oj’Neuroendocrinology, pp. 3 10-320. Springer-Verlag, Berlin. Lipton, J. M., and Glyn, J. R. (1980). Central administration of peptides alters thermoregulation in the rabbit. Peptides 1, 15-18. Martin, J. T., and van Wimersma Greidanus, Tj.B. (1979). Imprinting behavior: influence of vasopressin and ACTH analogues. Psychoneuroendocrinology. 3, 261-269. Moriya, K., and Itoh, S. (1969). Inhibition of adipose tissue lipase activity following administration of vasopressin. Japan. J. Physiol. 19, 8344840.
BRIEF REPORT
231
Okuno, A., Yamamoto, M., and Itoh, S. (1965). Lowering of the body temperature induced by vasopressin. Japan. J. Physiol. 15, 378-381. Papez, J. W. (1937). A proposed mechanism of emotion. Arch. Neurol. Psychiat. 38, 725-143. Tsukada, M., Okuno, A., and Itoh, S. (1965). Influence of vasopressin on the metabolic rate in rats. Japan. J. Physiol. 15, 388-396. van Ree, J. M., Bohus, B., Versteeg, D. H. G., and de Wied, D. (1978). Commentaries: neurohypophyseal principles and memory processes. Biochem. Pharmacol. 27, 17931800.
AND
BEHAVIOR
15,
226-231 (1981)
BRIEF REPORT Effect of Exogenous Arginine Vasopressin Temperature in the Albino Rat A. F. CRINE,*~‘*~ *Laboratory
of
S. BREDART,*
on Rectal
AND J. J. LEGROS~
Experimental Psychology and TNeuroendocrinology University of Likge. B4020 Ligge, Belgium
Section,
One subcutaneous injection of arginine vasopressin (2.0 I.U./kg.) in SpragueDawley male rats caused a decrease in rectal temperature. A slight fall was also noted in the placebo group but there were statistically significant differences. This result was discussed in terms of modification of emotional processes.
Since the early works on the effect of posterior hypophysectomy on acquired behavior (de Wied, 1965), vasopressin has been tested in behavioral situations such as active and passive avoidance conditioning (de Wied, 1971; Ader and de Wied, 1972; Bohus, Ader, and de Wied, 1972; de Wied, 1976a), appetitive maze conditioning (Bohus, 1977), and imprinting (Martin and van Wimersma Greidanus, 1979). Generally, vasopressin and its analogs induced an increased resistance to extinction, more rapid acquisition, and improved retention performance in avoidance and appetitive tests. These effects have been interpreted in terms of vasopressin effects on memory consolidation and retrieval of information (de Wied, 1976b; van Ree, Bohus, Versteeg, and de Wied, 1978; de Wied, 1979; de Wied and Bohus, 1979). We have measured the effects of systemic administration of arginine vasopressin (AVP) on body temperature in the rat. This type of investigation is not new since peripheral injections of lysine vasopressin have already been shown induce a fall in rectal temperature in the rat (Okuno, Yamamoto, and Itoh, 1965). More recently, Kasting, Veale, and Cooper (1980) have demonstrated a hypothermic effect of AVP after intraventricular administration. Moreover, intracerebral injections of AVP have been reported to reduce fever in sheep (Cooper, Kasting, Lederis, and ’ Aspirant FNRS. 2 To whom requests for reprints should be sent at: Laboratory of Experimental ogy, University of Liege, Blvd. de la Constitution, 32 Liege, Belgium. 226 0018-506X/81/020226-06$01.00/0 Copyright All rights
@ 1981 by Academic Press. Inc. of reproduction in any form reserved.
Psychol-
BRIEF
REPORT
227
Veale, 1979), and the increase in body temperature resulting from high environmental temperatures is related to an increase in plasma AVP in pigs (Forsling, Ingram, and Stanier, 1976). In addition, stimulation such as the increase in temperature at the beginning of spring induces a massive secretion of vasopressin in hibernants (Legait, Burlet, and Marchetti, 1970). Conversely, secretion of endogenous vasopressin induced by hypertonicity of circulating fluid can cause a temperature decrease (Gkuno et al., 1965). However, exogenously administered vasopressin does not suppress the increase of body temperature caused by heat exposure (Okuno ef al., 1965). Finally, in contrast to the finding of Kasting et al. (1980), Lipton and Glyn (1980) reported that intraventricular injections of AVP produced hyperthermia in the rabbit. Therefore, the role of vasopressin in the modulation of body temperature is not clear and this research was aimed at clarifying the relationship between vasopressin and body temperature. Methods. Subjects. Twenty-two male Sprague-Dawley rats (Animalabo, Brussels, Belgium) weighing 340-380 g at the beginning of the experiments were housed in groups. Food and water were available ad lib and the 1ight:dark cycle was IO:14 hr. Apparatus. A rectal thermometer (DU-3 ELLAB Copenhagen, Denmark) was used in this experiment. Its two probes allow the simultaneous measurement of temperatures in two animals. The apparatus in which each rat was maintained during temperature measurements is prismatic in shape, made of transparent Plexiglas, and has air-conducting holes on each side. The ambient room temperature was 26 2 1°C and experimental room was not soundproof. Procedure. Each rat was removed from its home cage, placed directly in the immobility apparatus, and the rectal thermometer was inserted. During the following 20 min, the animals were not subjected to any other treatment. This period permitted habituation to the apparatus. At the end of this period, the temperature was taken and the treatment given. The experimental group (n = 12) was injected subcutaneously with arginine vasopressin (SANDOZ) at a dose of 2.0 IU/kg in 5.0 ml saline. The placebo group (n = 10) was injected subcutaneously with NaClO.9%, 5.0 ml/kg, under the same conditions. Immediately after the injection, the rat was placed again in the immobility apparatus and the rectal probe reinserted. The temperature was measured for the second time as soon as the probe was reinserted; for the third time 10 min later, and then every 5 min until 90 min had passed. All measures were taken between 2 and 6 PM. Results. The change in rectal temperature over time for both experimental and control rats is presented in Fig. 1. The statistical analysis (Student’s test) shows a decrease in temperature in both groups. This decrease became significantly different from base line after 30 min in the
228
BRIEF
REPORT
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BRIEF
REPORT
229
group that received AVP (t(22) = -2.69; p < .02), and in the placebo group after 70 min (t(18) = -2.21;~ < .05). Furthermore, the decrease in temperature was significantly larger in the experimental group than in the placebo group between the 35th and the 55th min (t(20) = -2.65, -2.76, -2.26, -2.22, -2.33, respectively;p < .02 for the former twot’s andp < .05 for the latter three t’s). Discussion. An injection of 2.0 W/kg of arginine vasopressin induced a significant decrease in rectal temperature. Although a slight fall in rectal temperature was also seen in the placebo group, there were statistically significant differences between the two groups. In 1965, Okuno er al. reported similar effects after peripheral injection of lysine vasopressin. In 1980, Kasting et al. also noted a decrease in rectal temperature after intraventricular injections of AVP. However, contrary to our results (see Fig. 1) the rectal temperature of animals injected with vasopressin returned to base line after 90 and 40 min, respectively, and there was no decrease in rectal temperature in the placebo group. These two inconsistencies may be important in a further analysis of vasopressin as a hypothermic agent. It is possible that the apparatus used to immobilize the animals during the experiment is aversive and consequently can induce a rise in temperature as hyperthermic reaction can be a somatic response to aversive situations (Delini-Stula, 1970). The effect of vasopressin would not be a pure physiological effect, but rather, vasopressin may play the role of an adaptor to the aversive situation. In this case, vasopressin may decrease the aversity (= emotivity! ?) level. However, a peripheral interpretation for the modulation of body temperature by vasopressin was offered by Itoh, Tsukada, Okuno, and Yoshinari (1966), Itoh, Tsukada, and Omoe (1967), and Moriya and Itoh (1969). They hypothesized that the decrease in temperature results from a reduction in metabolic rate caused by a lowering of the plasma-free fatty acid level. In contrast, Cooper et al. (1979) found that the septal region is an important substratum for the vasopressin-induced decrease in fever. It is not yet clear whether the vasopressin effect on fever and on normal body,temperature is mediated by similar mechanisms. If such is the case, the interpretation offered here may be especially valid when it is recalled that septal region is a brain region that has been implicated in emotion (Papez, 1937). However, as long as reports of the effect of vasopressin on body temperature are conflicting (see results obtained by Kasting et al. (1980) vs Lipton and Glyn (1980)), this interpretation will remain very limited. Therefore, it is necessary to systematically reanalyze the effect of vasopressin and its analogs in several species, with wide range of doses, using both peripheral and central routes of administration, and variations in the ambient temperature before firm conclusions can be drawn.
230
BRIEF
REPORT
ACKNOWLEDGMENTS This
study
was supported
by Grant
3.4507.79
from
the Belgian
FRSM.
REFERENCES Ader,
R., and de Wied, D. (1972). Effects of lysine vasopressin on passive avoidance learning. Psychon. Sri. 29, 46-48. Bohus, B., Ader, R., and de Wied, D. (1972). Effects of vasopressin on active and passive avoidance behavior. Horm. Behav. 3, 191-197. Bohus, B. (1977). Effect of desglycinamide-lysine vasopressin (DG-LVP) on sexually motivated T-maze behavior in the male rat. Horm. Behav. 8, 52-61. Cooper, K. E., Kasting, N. W., Lederis, K., and Veale, W. L. (1979). Evidence supporting a role for endogenous vasopressin in natural suppression of fever in the sheep. J. Physiol. 295, 33-45. Delini-Stula, A. (1970). The development and the extinction of hyperthermia induced by conditioned avoidance behavior in rats. J. Exp. Anal. Behav. 14, 213-218. de Wied, D. (1965). The influence of the posterior and intermediate lobe of the pituitary and pituitary peptides on the maintenance of a conditioned avoidance response in rats. fnt. J. Neuropharmacol. 4, 157-167. de Wied, D. (1971). Long term effect of vasopressin on the maintenance of a conditioned avoidance response in rats. Nature (London) 232, 58-60. de Wied, D. (1976). Behavioral effects of intraventricularly administered vasopressin and vasopressin fragments. Lije Sci. 19, 685-690. (a) de Wied, D. (1976). Hormonal influences on motivation, learning and memory processes. Hosp. Pruct. 11, 123-131. (b) de Wied, D. (1979). Pituitary neuropeptides and behavior. In K. Juxe, T. Hokfelt, and R. Luft (Eds.), Central Regulation of the Endocrine System, pp. 297-314. Plenum, New York. de Wied, D., and Bohus, B. (1979). Modulation of memory processes by neuropeptides of hypothalamic-neurohypophyseal origin. In M. A. B. Brazier (Ed.), Brain Mechanisms in Memory and Learning: From the Single Neuron to Man, pp. 139-149. Raven Press. New York. Forsling, M. L., Ingram, D. M.. and Stanier, M. W. (1976). Effects of various ambient temperatures and of heating and cooling the hypothalamus and cervical spinal cord on antidiuretic hormone and urinary osmolahty. J. Physiol. 257, 673-686. Itoh, S., Tsukada, M., Okuno, A., and Yoshinari, T. (1966). Effects of vasopressin on the plasma concentration of free fatty acids and in vitro oxygen consumption of tissues of the rat. Japan. J. Physiol. 16, 23-30. Itoh, S., Tsukada, M., and Omoe, K. (1967). Effect of vasopressin on plasma lipids in the rat. Japan. J. Physiol. 17, 667-677. Kasting, N. W., Veale, W. L., and Cooper, K. E. (1980). Convulsive and hypothermic effects of vasopressin in the brain of the rat. Canad. J. Physiol. Pharmacol. 58, 316-319. Legait, E., Burlet, C., and Marchetti, J. (1970). Contribution a I’etude du systeme hypothalamo-neurohypophysaire au tours de I’hibernation. In W. Borgmann and B. Scharrer (Eds.),Aspecfs oj’Neuroendocrinology, pp. 3 10-320. Springer-Verlag, Berlin. Lipton, J. M., and Glyn, J. R. (1980). Central administration of peptides alters thermoregulation in the rabbit. Peptides 1, 15-18. Martin, J. T., and van Wimersma Greidanus, Tj.B. (1979). Imprinting behavior: influence of vasopressin and ACTH analogues. Psychoneuroendocrinology. 3, 261-269. Moriya, K., and Itoh, S. (1969). Inhibition of adipose tissue lipase activity following administration of vasopressin. Japan. J. Physiol. 19, 8344840.
BRIEF REPORT
231
Okuno, A., Yamamoto, M., and Itoh, S. (1965). Lowering of the body temperature induced by vasopressin. Japan. J. Physiol. 15, 378-381. Papez, J. W. (1937). A proposed mechanism of emotion. Arch. Neurol. Psychiat. 38, 725-143. Tsukada, M., Okuno, A., and Itoh, S. (1965). Influence of vasopressin on the metabolic rate in rats. Japan. J. Physiol. 15, 388-396. van Ree, J. M., Bohus, B., Versteeg, D. H. G., and de Wied, D. (1978). Commentaries: neurohypophyseal principles and memory processes. Biochem. Pharmacol. 27, 17931800.