Abstract
Male Sprague-Dawley rats were trained in a two-lever operant discrimination task using 20 mg/kg thyrotropin-releasing hormone (TRH) and saline as cues. Following completion of 40 daily training sessions, 22 of 25 subjects demonstrated a high level of discriminative responding based on the TRH and saline cues. An evaluation of the time course of TRH indicated that the stimulus properties peak between 5 and 15 min and dissipate substantially by 55–65 min. During additional testing, rats showed dose-dependent generalization between the training treatments (20 mg/kg TRH and saline) and novel doses of TRH (1, 5, 10, and 40 mg/kg). However, animals failed to show generalization between the training drug (20 mg/kg TRH) and d-amphetamine sulfate (0.8, 1.6, or 2.4 mg/kg); likewise, animals trained to discriminate d-amphetamine (0.8 or 1.6 mg/kg) from saline failed to show generalization between d-amphetamine and TRH (10, 20, or 30 mg/kg). Microgram quantities of TRH (2.5–25 μg) administered into either the lateral or third ventricle elicited dose-dependent generalization to the training drug (TRH 20 mg/kg, i.p.), suggesting a CNS mechanism of action for this effect of TRH.
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Barlow, T. S., Cooper, B. R., Breese, G. R., Prange, A. J., Jr., Lipton, M. A.: Effects of thyrotropin-releasing hormone on behavior: evidence for an anorexic-like action. Society for Neuroscience, 5th Annual Meeting, New York City, Abstract No. 519, P. 334 (1975)
Breese, G. R., Cooper, B. R., Prange, A. J., Jr., Cott, J. M., Lipton, M. A.: Interactions of thyrotropin-releasing hormone with centrally acting drugs. In: The thyroid axis, drugs and behavior (A. J. Prange, Jr., ed.), pp. 113–128. New York: Raven 1974a
Breese, G. R., Cott, J. M., Cooper, B. R., Prange, A. J., Jr., Lipton, M. A.: Antagonism of ethanol narcosis by thyrotropin releasing hormone. Life Sci. 14, 1053–1063 (1974b)
Breese, G. R., Cott, J. M., Cooper, B. R., Prange, A. J., Jr., Lipton, M. A., Plotnikoff, N. P.: Effects of thyrotropin releasing hormone (TRH) on the actions of pentobarbital and other centrally acting drugs. J. Pharmacol. Exp. Ther. 193, 11–22 (1975)
Brown, R. G., Harris, R. T., Ho, B. T.: Stimulus properties of mescaline and N-methylated derivatives: difference in peripheral and direct central administration. Psychopharmacologia (Berl.) 39, 43–56 (1974)
Gianutsos, G., Lal, H.: Effect of loperamide, haloperidol and methadone in rats trained to discriminate morphine from saline. Psychopharmacologia (Berl.) 41, 267–270 (1975)
Green, A. R., Grahame-Smith, D. C.: TRH potentiates behavioral changes following increased brain 5-hydroxytryptamine accumulation in rats. Nature 251, 524–526 (1974)
Hine, B., Sanghvi, I., Gershon, S.: Evaluation of thyrotropin-releasing hormone as a potential antidepressant agent in the conscious dog. Life Sci. 13, 1789–1797 (1973)
Hirschhorn, I. D., Hayes, R. L., Rosecrans, J. A.: Discriminative control of behavior by electrical stimulation of the dorsal raphe nucleus: generalization to lysergic acid diethylamide (LSD). Brain Res. 86, 134–138 (1975)
Horita, A., Carino, M. A.: Thyrotropin releasing hormone (TRH)-induced hyperthermia and behavioral excitation in rabbits. Fed. Proc. 34, 297 (1975)
Jones, C. N.: The stimulus properties of thyrotropin-releasing hormone. Dissertation Abstracts International (in press, 1978)
Jones, C. N., Hill, H. F., Harris, R. T.: Discriminative response control by d-amphetamine and related compounds in the rat. Psychopharmacologia (Berl.) 36, 347–356 (1973)
Jones, C. N., Grant, L. D., Prange, A. J., Jr., Breese, G. R.: Stimulus properties of d-amphetamine in the rat: interaction with thyrotropin-releasing hormone (TRH). Society for Neuroscience, New York City, Abstract No. 382, p. 246 (1975)
Jones, C. N., Grant, L. D., Vospalek, D. M.: Temporal parameters of d-amphetamine as a discriminative stimulus in the rat. Psychopharmacologia (Berl.) 46, 59–64 (1976)
König, J. F. R., Klippel, R. A.: The rat brain. Pluntington, New York: R. E. Kreiger 1974
Loosen, P. T., Wilson, I. C., Lara, P. P., Prange, A. J., Jr., Pettus, C.: The influence of thyrotropin-releasing hormone in the alcohol withdrawal syndrome. Arzneim. Forsch. 26, 1164–1166 (1976)
Metcalf, G.: TRH: a possible mediator of thermoregulation. Nature 252, 310–311 (1974)
Oliver, C., Ben-Jonathan, N., Mical, R. S., Porter, J. C.: Transport of thyrotropin-releasing hormone from cerebrospinal fluid to hypophyseal portal blood and the release of thyrotropin. Endocrinology 97, 1138–1143 (1975)
Overton, D. A.: Discriminative control by drug states. In: Stimulus properties of drugs (T. Thompson and R. Pickens, eds.), pp. 87–110. New York: Appleton-Century-Crofts 1971
Overton, D. A.: Experimental methods for the study of state-dependent learning. Fed. Proc. 33, 1800–1813 (1974)
Plotnikoff, N. P., Prange, A. J., Jr., Breese, G. R., Anderson, M. S., Wilson, I. C.: The effects of thyrotropin-releasing hormone on DOPA response in normal, hypophysectomized and thyroidectomized animals. In: The thyroid axis, drugs and behavior (A. J. Prange, Jr., ed.), pp. 103–113. New York: Raven 1974
Prange, A. J., Jr., Wilson, I. C., Lara, P. P., Alltop, L. B.: Effects of thyrotropin-releasing hormone in depression. In: The thyroid axis, drugs and behavior (A. J. Prange, Jr., ed.), pp. 135–145. New York: Raven 1974
Prange, A. J., Jr., Breese, G. R., Jahnke, G. D., Martin, B. R., Cooper, B. R., Cott, J. M., Wilson, I. C., Alltop, L. B., Lipton, M. A., Bissette, G., Nemeroff, C. B., Loosen, P. T.: Modification of pentobarbital effects by natural and synthetic polypeptides: dissociation of brain and pituitary effects. Life Sci. 16, 1907–1914 (1975)
Prange, A. J., Jr., Nemeroff, C. B., Lipton, M. A., Breese, G. R., Wilson, I. C.: Peptides and the central nervous system. In: Handbook of psychopharmacology (L. L. Iversen, S. D. Iversen, and S. H. Snyder, eds.), Vol. 13. New York: Plenum (in press), 1978)
Richards, D. W., III, Harris, R. T., Ho, B. T.: Central control of d-amphetamine induced discriminative stimuli. Society for Neuroscience Meeting, Abstract 59.1, p. 340 (1973)
Schechter, M. D.: Transfer of state-dependent control of discriminative behavior between subcutaneously and intraventricularly administered nicotine and saline. Psychopharmacologia (Berl.) 32, 327–335 (1973)
Segel, D. S., Mandell, A. J.: Differential behavioral effects of hypothalamic polypeptides. In: The thyroid axis drugs and behavior (A. J. Prange, Jr., ed.), pp. 129–133. New York: Raven 1974
Shannon, H. E., Holtzman, S. G.: Evaluation of the discriminative effects of morphine in the rat. J. Pharmacol. Exp. Ther. 198, 54–56 (1976)
Tiwary, C. N., Rosenbloom, A. L., Robertson, M. F., Parker, J. C.: Improved behavior of hyperkinetic children given TRH. Soc. Psychoneuroendocrinol. 4th Int. Cong. (1973)
Waters, W. H., Richards, D. W., Harris, R. T.: Discriminative control and generalization of the stimulus properties of dl-amphetamine in the rat. In: Drug addiction: experimental pharmacology, vol. 1 (J. M. Singh, L. H. Miller, and H. Lal, eds.), pp. 3–16. New York:Futura 1972
Wei, E., Sigel, S., Loh, H., Way, E. L.: Thyrotropin releasing hormone and shaking behavior in rats. Nature 253, 739–740 (1975)
Wilson, I. C., Lara, P. P., and Prange, A. J., Jr.: Thyrotropin-releasing hormone in schizophrenics. Lancet 1973a II, 43–44
Wilson, I. C., Prange, A. J., Jr., Lara, P. P., Alltop, L. B., Stikeleather, R. A., Lipton, M. A.: TRH (lopremone): psychobiological responses of normal women. I. Subjective experiences. Arch. Gen. Psychiatry 29, 15–21 (1973b)
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Jones, C.N., Grant, L.D. & Prange, A.J. Stimulus properties of thyrotropin-releasing hormone. Psychopharmacology 59, 217–224 (1978). https://doi.org/10.1007/BF00426625
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DOI: https://doi.org/10.1007/BF00426625