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Amphetamine actions in dorsolateral tegmental rats: Hypodipsia, anorexia, and central nervous system permeation to [14C]amphetamine
BEHAVIORAL AND NEURAL BIOLOGY
35, 64-69 (1982)
BRIEF REPORT Amphetamine Actions in Dorsolateral Tegmental Rats: Hypodipsia, Anorexia, and Central Nervous System Permeation to [t4C]Amphetamine PAUL J. WELLMAN, 1 DONALD E. CLARK, JAMES K . ROGERS, AND JAMES C. THOMAS2 Department of Psychology, Texas A&M University, College Station, Texas and United
States Department of Agriculture, College Station, Texas 77843 Electrolytic lesions of the dorsolateral tegmentum produced hyperdipsia, enhanced amphetamine-induced hypodipsia, yet attenuated amphetamine-induced anorexia. Central nervous system permeation by [~4C]amphetamine was comparable in control, operated control, and tegmental rats. These data suggest that (a) a common motivational process, such as malaise, cannot explain the anorexic and hypodipsic properties of amphetamine and (b) that the influence of tegmental damage on amphetamine actions did not result from differences in brain amphetamine levels.
The notion that amphetamine induces satiety via a catecholaminergic mechanism within the lateral hypothalamus (Ahlskog & Hoebel, 1973; Leibowitz, 1980) implies that the anorexic action of amphetamine ought to be specific to feeding. Carey and Goodall (1974), however, noted that amphetamine induced dose-dependent hypodipsia in rats. Moreover, the observation that amphetamine produces conditioned taste aversion at dosage levels that produce anorexia and hypodipsia (Berger, 1972; Carey & Goodall, 1974) suggests that a nonspecific factor may produce each effect. Lesions of the dorsolateral tegmentum (DLT) attenuate both the anorexia and the taste aversion induced by amphetamine (Wellman & Peters, 1980; Wellman, Mclntosh, & Guidi, 1981. The present experiment sought to further examine a nonspecific conception of amphetamineinduced anorexia by assessing the influence of tegmentat lesions on the hypodipsia (0.5, 1.0, and 2.0 mg/kg) and the anorexia (2.0 mg/kg) induced by amphetamine. To the extent that a common motivational process, perhaps malaise, mediates these amphetamine effects, tegmental lesions ought to attenuate both amphetamine-induced anorexia and hypodipsia. To whom requests for reprints should be addressed. z The authors wish to thank Nancy Byer for her excellent technical assistance in carrying out the liquid scintillation procedures.
64 0163-1047/82/050064-06502.00/0 Copyright © 1982 by Academic Press, Inc. All rights of reproduction in any form reserved.
A M P H E T A M I N E ACTION IN TEGMENTAL RATS
65
Were such an outcome to be observed, however, it need not imply that malaise is the common substrate mediating amphetamine-induced anorexia, hypodipsia, and taste aversion. An implicit assumption of previous work (e.g., Ahlskog & Hoebel, 1973; Wellman & Peters, 1980) is that permeation of central ependymal cells to amphetamine is identical in control and tegmental rats. If, however, tegmental lesions were to produce a decline in brain permeation by amphetamine, these lesions might be expected to attenuate actions of amphetamine that are mediated by the central nervous system. The notion that tegmental rats display attenuated amphetamine-induced anorexia simply because less amphetamine enters their brains was also examined in the present experiment by assessing the uptake of intraperitoneally administered [14C]amphetamine sulfate (2.0 mg/kg) into the central nervous systems of control, operated control, and tegmental rats. The animals were 21 female hooded Long-Evans rats (Blue Spruce Farms) 90 days old and weighing 260-3t7 g at the beginning of the experiment. The rats were individually housed in standard plastic cages (Lab. Co.) containing pine shavings in a temperature-controlled (23°C) colony room under continuous incandescent illumination. A saline solution consisted of 0.9% sodium chloride in sterile distilled water, whereas amphetamine solutions were prepared by dissolving dextro-amphetamine sulfate (Sigma Chemical Co.) into sterile distilled water. [propyl-l-14C]Amphetamine (9.3 mC/mM; California Bionuclear Corp., Sun Valley, Calif.) was added to 2.0 mg/ml stock amphetamine sulfate to achieve a final specific activity of 0.17 ~Ci/mM. The rats were maintained on a 23-hr water deprivation schedule on Days 1-8 with food available ad libitum in the home cage during the water deprivation intervals. Tap water was made available during a 60min period on each day from calibrated drinking tubes suspended from the wire-mesh roof of a separate plastic test cage. Tegmental lesions were produced on Day 9 for 14 rats using procedures described elsewhere (Wellman & Peters, 1980); seven rats served as sham-operated control rats. Free access to food and water was allowed for 3 days to facilitate recovery of body weight lost during the deprivation procedure prior to and following surgery. During Days 1 through 4 following the recovery period, the 23-hr water deprivation schedule was reinstated and each rat received an injection of saline (1.0 ml/kg ip) 30 min prior to each drinking test. The amphetamine test sequence was carried out on Days 5 through 11 and consisted of alternating amphetamine and saline tests: amphetamine (Days 5, 7, 9, 11); saline (Days 6, 8, 10). For the amphetamine tests, drug injections (0.5, 1.0, and 2.0 mg/kg ip) were given 30 min prior to water access. All rats received each amphetamine dosage once, with drug order randomized for each group to minimize order effects. Water intake was measured to the nearest 1.0 ml.
66
WELLMAN ET AL.
The influence of tegmental lesions on amphetamine anorexia was also examined. On 3 consecutive days, the rats were maintained on a 23-hr food deprivation schedule and were given daily access to a high-fat diet (33% melted vegetable oil and 66% ground chow) in separate eating cages for 60 min. Saline injections (1.0 ml/kg) preceded each food intake test by 30 min. On Day 4, all rats were injected with 2.0 mg/kg amphetamine (ip) 30 min prior to the food intake test. All intakes (corrected for spillage) were recorded to the nearest 0.10 g. A 14-day period separated the end of the food intake procedures and the assessment of central nervous system permeation by [~4C]amphetamine. On the test day, each rat received a single ip injection of [~4C]amphetamine (2.0 mg/0.90 mCi/kg). At 60 rain postinjection, each rat was rendered unconscious with carbon dioxide and decapitated. Trunk blood samples (approximately 1.0 ml) were stored in heparinized tubes until liquid scintillation (LSC) analysis. Brains were dissected from the calvarium and were sectioned into fore-, mid-, and hindbrain samples. Fore- and hindbrain tissue blocks were combined, blotted dry, weighted and air dried until LSC analysis. After fixation in 10% formalin (96 hr), the midbrain blocks containing the tegmental lesions were evaluated using procedures described elsewhere (Wellman & Peters, 1980). A Beckman LS-3133T spectrometer (Beckman Instruments, Fullerton, Calif.) equipped for external standardization was used for liquid scintillation counting. A toluene-based scintillation cocktail was used in which 2-methoxyethanol was used to improve miscibility with aqueous samples. All LSC measurements were corrected for background, quench, and combustion efficiency. From each blood sample, 0.25-ml aliquots of plasma were added to vials containing 20 ml scintillation cocktail. The vials were held in the dark for at least 24 hr for depletion of photoluminescence and then the radioactivity was quantitated by LSC. Air-dried samples of brain (approximately 0.5 g) were combusted under 1 atmosphere of oxygen iv_ a modified Packard Tri-Carb sample oxidizer (Packard Instrument Co., Downers Grove, Ill.). Combustion gases were bubbled through a carbon dioxide trapping solution (equal volumes of 2-aminoethanol and 2-methoxyethanol), and the trapped radiocarbon was then quantitated by LSC. Microscopic examination of the lesions, using coded procedures, revealed misplacement (unilateral and dorsal) in eight rats; their data were therefore included in the statistical analyses as operated controls. The remaining six rats sustained bilateral, symmetrical destruction localized within the dorsolateral aspects of the tegmentum comparable to those reported earlier (Wellman & Peters, 1980). Percent change analyses (from average saline baseline) were used because tegmental rats drank significantly more water (F (2, 18) = 4.1, p < .01) than control and operated control rats after saline treatment
AMPHETAMINE ACTION IN TEGMENTAL RATS WATER
67
FOOD
25 Z Z 50 D
75
100
C 171 0.5
1.0
2.0
0 2.0
mg/kg A M P H E T A M I N E
Flo. 1. Mean group percent suppression (from saline baseline) of water intake and of high-fat intake produced by 0.5, 1.0, and 2.0 mg/kg amphetamine in control (C), operated control (O), and dorsolateral tegmental (D) rats.
(Fig. 1). Amphetamine produced comparable dose-dependent, significant suppressions of water intake (F(2, 36) = 24.4, p < .0001) in control and operated control rats. Tegmental rats displayed significantly larger percent suppressions of water intake than control and operated control rats to a 0.05 mg/kg amphetamine dosage (t(ll) = 2.3, t(12) = 2.2, respectively, p < .05), but no significant between-group differences were observed at higher amphetamine concentrations. Tegmental rats ate slightly, but not significantly, more of the high-fat diet than control and operated control rats after saline treatment (X = 12.1, 11.0, 11.4 g, respectively). In contrast to the hypodypsia outcomes, tegmental rats displayed significant attenuation of amphetamine-induced anorexia (Fig. 1). The 2.0-mg/kg amphetamine dosage suppressed food intake to approximately 6% of baseline values in control and operated control rats, whereas the food intakes of tegmental rats were reduced to only 37% of baseline values (F(2, 28) = 13.9, p < .0002). Table 1 presents the mean group levels of [laC]amphetamine (expressed as parts per million (ppm)) in blood and brain samples from control, operated control, and tegmental rats. There was a slight, but nonsignificant, trend for tegmental rats to display higher levels of [14C]amphetamine in both blood and brain samples than those of controls and operated controls. This trend, however, was in a direction opposite to that predicted (i.e., lower brain levels of amphetamine in tegmental rats). Miller (1957) argued that the proper assessment of motivation required comparisons of data from numerous paradigms. The present experiment is one of a series designed to elucidate the precise nature of the amphetamine substrate altered by tegmental damage. The simplest expla-
68
WELLMAN ET AL. TABLE 1 Group Mean Levels Radiocarbon in Plasma and Brain from Control, Operated Control, and Tegmental Rats Sacrificed 1 Hr Following Injection of d-[~4C] amphetamine ° Amphetamine levels (ppm) b
Group
N
){ Plasma SEM
Control Operated control Tegmental
7 8 6
0.54 --- .05 0.53 _+ .08 0.58 _+ .09
X
Brain SEM
2.14 _+ .27 2.14 _+ .25 2.23 _+ .22
a Single ip injection with d-[~4C]amphetamine sulfate, 2 mg/kg. b Parts per million (l~g amphetamine equivalent/ ml plasma; ~g amphetamine equivalent/g brain (wet weight). It should be noted that these values represent the total amount of radiocarbon present in each sample. ~4C detected was presumably associated with the parent amphetamine compound (Young & Gordon, 1962).
nation, namely that amphetamine-induced anorexia reflects simply aversive properties, was supported by the early demonstrations that tegmental lesions attenuate both amphetamine-induced anorexia and conditioned taste aversion, but not by the present demonstration that tegmental lesions do not attenuate amphetamine-induced hypodipsia. These differential outcomes support the suggestion of Leibowitz (1980) that a common process does not mediate amphetamine-induced anorexia and hypodipsia. Morever, the present differential outcomes may lend credence to Carey and Goodall's (1974) suggestion that amphetamine-induced taste aversion may simply result from conditioning of the satiety property of amphetamine. The precise nature of amphetamine-induced hypodipsia, however, was not clarified by the present study. The present data suggest that brain permeation by amphetamine is unaltered in control, operated control, and in dorsolateral tegmental rats. This finding, along with the failure of tegmental lesions to attenuate amphetamine-induced hypodipsia, suggests that the action of these lesions on amphetamine activity is specific rather than nonspecific. Tegmental rats display attenuated amphetamine anorexia not because fewer amphetamine molecules enter their brains but rather because a mechanism critical for the expression of anorexia has been partially damaged.
AMPHETAMINE ACTION IN TEGMENTAL RATS
69
REFERENCES Ahlskog, J. E., & Hoebel, B. S. (1973). Overeating and obesity from damage to a noradrenergic system in the brain. Science, 182, 166-168. Berger, D. D. (1972). Conditioning of food aversions by injections of psychoactive drugs. Journal of Comparative and Physiological Psychology, 81, 21-25. Carey, R. J., & Goodall, E. B. (1974). Amphetamine-induced taste aversion: A comparison of d versus 1-amphetamine. Pharmacology, Biochemistry and Behavior, 2, 325-330. Kornblith, C. L., & Hoebel, B. G. (1976). A dose-response study of anorectic drug effects on food intake, self-stimulation and stimulation-escape. Pharmacology, Biochemistry and Behavior, 5, 215-218. Leibowitz, S. F. (1975). Catecholaminergic adrenergic mechanisms of the lateral hypothalamus: Their role in the mediation of amphetamine anorexia. Brain Research, 98, 529-545. Leibowitz, S. F. (1980). Neurochemical systems of the hypothalamus in control of feeding and drinking behavior and water-electrolyte excretion. In P. J. Morgane & J. Panksepp (Eds.), Handbook of the Hypothalamus, Vol. 3A, pp. 299-407. New York: Dekker. Miller, N. E. (1957). Experiments on motivation. Science, 126, 1271-1278. Wellman, P. J., Mclntosh, P., & Guidi, E. (1981). Effects of dorsolateral tegmental lesions on amphetamine- and lithium-induced taste aversions. Physiology and Behavior, 26, 341-344. Wellman, P. J., & Peters, R. H. (1980). Effects of amphetamine and phenylpropanolamine on food intake in rats with ventromedial hypothalamic or dorsolateral tegmental damage. Physiology and Behavior, 25, 819-827. Young, R. L., & Gordon, M. W. (1962). The disposition of [14C]amphetamine in the rat. Journal of Neurochemistry, 9, 161-167.
35, 64-69 (1982)
BRIEF REPORT Amphetamine Actions in Dorsolateral Tegmental Rats: Hypodipsia, Anorexia, and Central Nervous System Permeation to [t4C]Amphetamine PAUL J. WELLMAN, 1 DONALD E. CLARK, JAMES K . ROGERS, AND JAMES C. THOMAS2 Department of Psychology, Texas A&M University, College Station, Texas and United
States Department of Agriculture, College Station, Texas 77843 Electrolytic lesions of the dorsolateral tegmentum produced hyperdipsia, enhanced amphetamine-induced hypodipsia, yet attenuated amphetamine-induced anorexia. Central nervous system permeation by [~4C]amphetamine was comparable in control, operated control, and tegmental rats. These data suggest that (a) a common motivational process, such as malaise, cannot explain the anorexic and hypodipsic properties of amphetamine and (b) that the influence of tegmental damage on amphetamine actions did not result from differences in brain amphetamine levels.
The notion that amphetamine induces satiety via a catecholaminergic mechanism within the lateral hypothalamus (Ahlskog & Hoebel, 1973; Leibowitz, 1980) implies that the anorexic action of amphetamine ought to be specific to feeding. Carey and Goodall (1974), however, noted that amphetamine induced dose-dependent hypodipsia in rats. Moreover, the observation that amphetamine produces conditioned taste aversion at dosage levels that produce anorexia and hypodipsia (Berger, 1972; Carey & Goodall, 1974) suggests that a nonspecific factor may produce each effect. Lesions of the dorsolateral tegmentum (DLT) attenuate both the anorexia and the taste aversion induced by amphetamine (Wellman & Peters, 1980; Wellman, Mclntosh, & Guidi, 1981. The present experiment sought to further examine a nonspecific conception of amphetamineinduced anorexia by assessing the influence of tegmentat lesions on the hypodipsia (0.5, 1.0, and 2.0 mg/kg) and the anorexia (2.0 mg/kg) induced by amphetamine. To the extent that a common motivational process, perhaps malaise, mediates these amphetamine effects, tegmental lesions ought to attenuate both amphetamine-induced anorexia and hypodipsia. To whom requests for reprints should be addressed. z The authors wish to thank Nancy Byer for her excellent technical assistance in carrying out the liquid scintillation procedures.
64 0163-1047/82/050064-06502.00/0 Copyright © 1982 by Academic Press, Inc. All rights of reproduction in any form reserved.
A M P H E T A M I N E ACTION IN TEGMENTAL RATS
65
Were such an outcome to be observed, however, it need not imply that malaise is the common substrate mediating amphetamine-induced anorexia, hypodipsia, and taste aversion. An implicit assumption of previous work (e.g., Ahlskog & Hoebel, 1973; Wellman & Peters, 1980) is that permeation of central ependymal cells to amphetamine is identical in control and tegmental rats. If, however, tegmental lesions were to produce a decline in brain permeation by amphetamine, these lesions might be expected to attenuate actions of amphetamine that are mediated by the central nervous system. The notion that tegmental rats display attenuated amphetamine-induced anorexia simply because less amphetamine enters their brains was also examined in the present experiment by assessing the uptake of intraperitoneally administered [14C]amphetamine sulfate (2.0 mg/kg) into the central nervous systems of control, operated control, and tegmental rats. The animals were 21 female hooded Long-Evans rats (Blue Spruce Farms) 90 days old and weighing 260-3t7 g at the beginning of the experiment. The rats were individually housed in standard plastic cages (Lab. Co.) containing pine shavings in a temperature-controlled (23°C) colony room under continuous incandescent illumination. A saline solution consisted of 0.9% sodium chloride in sterile distilled water, whereas amphetamine solutions were prepared by dissolving dextro-amphetamine sulfate (Sigma Chemical Co.) into sterile distilled water. [propyl-l-14C]Amphetamine (9.3 mC/mM; California Bionuclear Corp., Sun Valley, Calif.) was added to 2.0 mg/ml stock amphetamine sulfate to achieve a final specific activity of 0.17 ~Ci/mM. The rats were maintained on a 23-hr water deprivation schedule on Days 1-8 with food available ad libitum in the home cage during the water deprivation intervals. Tap water was made available during a 60min period on each day from calibrated drinking tubes suspended from the wire-mesh roof of a separate plastic test cage. Tegmental lesions were produced on Day 9 for 14 rats using procedures described elsewhere (Wellman & Peters, 1980); seven rats served as sham-operated control rats. Free access to food and water was allowed for 3 days to facilitate recovery of body weight lost during the deprivation procedure prior to and following surgery. During Days 1 through 4 following the recovery period, the 23-hr water deprivation schedule was reinstated and each rat received an injection of saline (1.0 ml/kg ip) 30 min prior to each drinking test. The amphetamine test sequence was carried out on Days 5 through 11 and consisted of alternating amphetamine and saline tests: amphetamine (Days 5, 7, 9, 11); saline (Days 6, 8, 10). For the amphetamine tests, drug injections (0.5, 1.0, and 2.0 mg/kg ip) were given 30 min prior to water access. All rats received each amphetamine dosage once, with drug order randomized for each group to minimize order effects. Water intake was measured to the nearest 1.0 ml.
66
WELLMAN ET AL.
The influence of tegmental lesions on amphetamine anorexia was also examined. On 3 consecutive days, the rats were maintained on a 23-hr food deprivation schedule and were given daily access to a high-fat diet (33% melted vegetable oil and 66% ground chow) in separate eating cages for 60 min. Saline injections (1.0 ml/kg) preceded each food intake test by 30 min. On Day 4, all rats were injected with 2.0 mg/kg amphetamine (ip) 30 min prior to the food intake test. All intakes (corrected for spillage) were recorded to the nearest 0.10 g. A 14-day period separated the end of the food intake procedures and the assessment of central nervous system permeation by [~4C]amphetamine. On the test day, each rat received a single ip injection of [~4C]amphetamine (2.0 mg/0.90 mCi/kg). At 60 rain postinjection, each rat was rendered unconscious with carbon dioxide and decapitated. Trunk blood samples (approximately 1.0 ml) were stored in heparinized tubes until liquid scintillation (LSC) analysis. Brains were dissected from the calvarium and were sectioned into fore-, mid-, and hindbrain samples. Fore- and hindbrain tissue blocks were combined, blotted dry, weighted and air dried until LSC analysis. After fixation in 10% formalin (96 hr), the midbrain blocks containing the tegmental lesions were evaluated using procedures described elsewhere (Wellman & Peters, 1980). A Beckman LS-3133T spectrometer (Beckman Instruments, Fullerton, Calif.) equipped for external standardization was used for liquid scintillation counting. A toluene-based scintillation cocktail was used in which 2-methoxyethanol was used to improve miscibility with aqueous samples. All LSC measurements were corrected for background, quench, and combustion efficiency. From each blood sample, 0.25-ml aliquots of plasma were added to vials containing 20 ml scintillation cocktail. The vials were held in the dark for at least 24 hr for depletion of photoluminescence and then the radioactivity was quantitated by LSC. Air-dried samples of brain (approximately 0.5 g) were combusted under 1 atmosphere of oxygen iv_ a modified Packard Tri-Carb sample oxidizer (Packard Instrument Co., Downers Grove, Ill.). Combustion gases were bubbled through a carbon dioxide trapping solution (equal volumes of 2-aminoethanol and 2-methoxyethanol), and the trapped radiocarbon was then quantitated by LSC. Microscopic examination of the lesions, using coded procedures, revealed misplacement (unilateral and dorsal) in eight rats; their data were therefore included in the statistical analyses as operated controls. The remaining six rats sustained bilateral, symmetrical destruction localized within the dorsolateral aspects of the tegmentum comparable to those reported earlier (Wellman & Peters, 1980). Percent change analyses (from average saline baseline) were used because tegmental rats drank significantly more water (F (2, 18) = 4.1, p < .01) than control and operated control rats after saline treatment
AMPHETAMINE ACTION IN TEGMENTAL RATS WATER
67
FOOD
25 Z Z 50 D
75
100
C 171 0.5
1.0
2.0
0 2.0
mg/kg A M P H E T A M I N E
Flo. 1. Mean group percent suppression (from saline baseline) of water intake and of high-fat intake produced by 0.5, 1.0, and 2.0 mg/kg amphetamine in control (C), operated control (O), and dorsolateral tegmental (D) rats.
(Fig. 1). Amphetamine produced comparable dose-dependent, significant suppressions of water intake (F(2, 36) = 24.4, p < .0001) in control and operated control rats. Tegmental rats displayed significantly larger percent suppressions of water intake than control and operated control rats to a 0.05 mg/kg amphetamine dosage (t(ll) = 2.3, t(12) = 2.2, respectively, p < .05), but no significant between-group differences were observed at higher amphetamine concentrations. Tegmental rats ate slightly, but not significantly, more of the high-fat diet than control and operated control rats after saline treatment (X = 12.1, 11.0, 11.4 g, respectively). In contrast to the hypodypsia outcomes, tegmental rats displayed significant attenuation of amphetamine-induced anorexia (Fig. 1). The 2.0-mg/kg amphetamine dosage suppressed food intake to approximately 6% of baseline values in control and operated control rats, whereas the food intakes of tegmental rats were reduced to only 37% of baseline values (F(2, 28) = 13.9, p < .0002). Table 1 presents the mean group levels of [laC]amphetamine (expressed as parts per million (ppm)) in blood and brain samples from control, operated control, and tegmental rats. There was a slight, but nonsignificant, trend for tegmental rats to display higher levels of [14C]amphetamine in both blood and brain samples than those of controls and operated controls. This trend, however, was in a direction opposite to that predicted (i.e., lower brain levels of amphetamine in tegmental rats). Miller (1957) argued that the proper assessment of motivation required comparisons of data from numerous paradigms. The present experiment is one of a series designed to elucidate the precise nature of the amphetamine substrate altered by tegmental damage. The simplest expla-
68
WELLMAN ET AL. TABLE 1 Group Mean Levels Radiocarbon in Plasma and Brain from Control, Operated Control, and Tegmental Rats Sacrificed 1 Hr Following Injection of d-[~4C] amphetamine ° Amphetamine levels (ppm) b
Group
N
){ Plasma SEM
Control Operated control Tegmental
7 8 6
0.54 --- .05 0.53 _+ .08 0.58 _+ .09
X
Brain SEM
2.14 _+ .27 2.14 _+ .25 2.23 _+ .22
a Single ip injection with d-[~4C]amphetamine sulfate, 2 mg/kg. b Parts per million (l~g amphetamine equivalent/ ml plasma; ~g amphetamine equivalent/g brain (wet weight). It should be noted that these values represent the total amount of radiocarbon present in each sample. ~4C detected was presumably associated with the parent amphetamine compound (Young & Gordon, 1962).
nation, namely that amphetamine-induced anorexia reflects simply aversive properties, was supported by the early demonstrations that tegmental lesions attenuate both amphetamine-induced anorexia and conditioned taste aversion, but not by the present demonstration that tegmental lesions do not attenuate amphetamine-induced hypodipsia. These differential outcomes support the suggestion of Leibowitz (1980) that a common process does not mediate amphetamine-induced anorexia and hypodipsia. Morever, the present differential outcomes may lend credence to Carey and Goodall's (1974) suggestion that amphetamine-induced taste aversion may simply result from conditioning of the satiety property of amphetamine. The precise nature of amphetamine-induced hypodipsia, however, was not clarified by the present study. The present data suggest that brain permeation by amphetamine is unaltered in control, operated control, and in dorsolateral tegmental rats. This finding, along with the failure of tegmental lesions to attenuate amphetamine-induced hypodipsia, suggests that the action of these lesions on amphetamine activity is specific rather than nonspecific. Tegmental rats display attenuated amphetamine anorexia not because fewer amphetamine molecules enter their brains but rather because a mechanism critical for the expression of anorexia has been partially damaged.
AMPHETAMINE ACTION IN TEGMENTAL RATS
69
REFERENCES Ahlskog, J. E., & Hoebel, B. S. (1973). Overeating and obesity from damage to a noradrenergic system in the brain. Science, 182, 166-168. Berger, D. D. (1972). Conditioning of food aversions by injections of psychoactive drugs. Journal of Comparative and Physiological Psychology, 81, 21-25. Carey, R. J., & Goodall, E. B. (1974). Amphetamine-induced taste aversion: A comparison of d versus 1-amphetamine. Pharmacology, Biochemistry and Behavior, 2, 325-330. Kornblith, C. L., & Hoebel, B. G. (1976). A dose-response study of anorectic drug effects on food intake, self-stimulation and stimulation-escape. Pharmacology, Biochemistry and Behavior, 5, 215-218. Leibowitz, S. F. (1975). Catecholaminergic adrenergic mechanisms of the lateral hypothalamus: Their role in the mediation of amphetamine anorexia. Brain Research, 98, 529-545. Leibowitz, S. F. (1980). Neurochemical systems of the hypothalamus in control of feeding and drinking behavior and water-electrolyte excretion. In P. J. Morgane & J. Panksepp (Eds.), Handbook of the Hypothalamus, Vol. 3A, pp. 299-407. New York: Dekker. Miller, N. E. (1957). Experiments on motivation. Science, 126, 1271-1278. Wellman, P. J., Mclntosh, P., & Guidi, E. (1981). Effects of dorsolateral tegmental lesions on amphetamine- and lithium-induced taste aversions. Physiology and Behavior, 26, 341-344. Wellman, P. J., & Peters, R. H. (1980). Effects of amphetamine and phenylpropanolamine on food intake in rats with ventromedial hypothalamic or dorsolateral tegmental damage. Physiology and Behavior, 25, 819-827. Young, R. L., & Gordon, M. W. (1962). The disposition of [14C]amphetamine in the rat. Journal of Neurochemistry, 9, 161-167.