Abstract
Reinforcing effects of intraperitoneally (IP) administered substance P (SP1-11), its amino-terminal fragment SP1-7 (SPN) and an analog of the carboxy terminus (pGlu6-SP6-11: SPC) were studied in rats. Two conditioned place preference paradigms were used. After three pairings of the drug with a certain environment the effect of the treatment was evaluated in the drug-free state during a test trial. The reinforcing effects of SP (37 nmol) and the equimolar dose of SPC were expressed by a significant increase in the amount of time the animals spent in the treatment environment. Other doses of SP (3.7 and 185 nmol) and SPC (7.4 and 185 nmol) and none of the doses of SPN (37, 185, 370 nmol) influenced the place preference behavior of the rats. The reinforcing effects of SP parallel the known facilitating effects of peripherally administered SP on memory. The amino acids that encode the reinforcing effects of SP may lie within the C-terminal sequence of the SP molecule.
Similar content being viewed by others
References
Banks WA, Kastin AJ (1985) Peptides and the blood-brain barrier: lipophilicity as a predictor of permeability. Brain Res Bull 15:287–292
Bardo MT, Miller JS, Neisewander JL (1984) Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR. Pharmacol Biochem Behav 21:545–549
Blumberg S, Teichberg VI (1982) The role of the N-terminal sequence in the biological activities of substance P. In: Costa E, Trabucchi M (eds) Regulatory peptides: from molecular biology to function. Raven Press, New York, pp 445–452
Bozarth MA (1987) Methods of assessing the reinforcing properties of abused drugs. Springer, New York
Bradbury MW (1989) Transport across the blood-brain barrier. In: Neuwelt EA (ed) Implications of the blood-brain barrier and its manipulation, vol 1. Plenum Press, New York, pp 119–136
Bury RW, Mashford ML (1976) Biological activity of C-terminal partial sequences of substance P. J Med Chem 19:854–856
Costa M (1988) Tachykinins in the sensory and peripheral nervous system. Regul Peptides 22:3–5
Couture R, Fournier A, Magnan J, St-Pierre S, Regoli D (1979) Structure activity studies on substance P. Can J Physiol Pharmacol 57:1427–1436
De Wied D, Jolles J (1982) Neuropeptides derived from proopiomelanocortin: behavioral, physiological and neurochemical effects. Physiol Rev 62:976–1059
Edvinsson L, Rosendal-Helgesen R, Uddman R (1983) Substance P: localization, concentration and release in cerebral arteries, choroid plexus and dura mater. Cell Tissue Res 234:1–7
Elliott PJ (1988) Place aversion induced by the substance P analogue, dimethyl-C7, is not state dependent: implication of substance P in aversion. Exp Brain Res 73:354–356
Gaffori O, Stewart JM, De Wied D (1984) Influence of substance P and fragments on passive avoidance behavior. Experientia 40:89–91
Gold PE (1986) The use of avoidance training in studies of modulation of memory storage. Behav Neural Biol 46:87–98
Hall ME, Stewart JM (1983) Substance P and behavior: opposite effects of N-terminal and C-terminal fragments. Peptides 4:763–768
Hall ME, Stewart JM (1984) Modulation of isolation-induced fighting by N- and C-terminal analogs of substance P: evidence for multiple recognition sites. Peptides 5:85–89
Hall ME, Miley FB, Stewart JM (1987a) Modulation of blood pressure by substance P: opposite effects of N- and C-terminal fragments on anesthesized rats. Life Sci 40:1909–1914
Hall ME, Grantham P, Limoli J, Stewart JM (1987b) Effects of substance P and neurokinin A (substance K) on motor behavior: unique effect of substance P attributable to its amino-terminal sequence. Brain Res 420:82–94
Hasenöhrl RU, Oitzl M-S, Huston JP (1989) Conditioned place preference in the corral: a procedure for measuring reinforcing properties of drugs. J Neurosci Meth 30:141–146
Holzhäuer-Oitzl M-S, Boucke K, Huston JP (1987) Reinforcing properties of substance P in the lateral hypothalamus revealed by conditioned place preference. Pharmacol Biochem Behav 28:511–515
Holzhäuer-Oitzl M-S, Hasenöhrl R, Huston JP (1988) Reinforcing properties of substance P in the region of the nucleus basalis magnocellularis in rats. Neuropharmacology 27:749–756
Huston JP, Oitzl M-S (1989) The relationship between reinforcement and memory: parallels in the rewarding and mnemonic effects of the neuropeptide substance P. Neurosci Biobehav Rev 13:171–180
Huston JP, Stäubli U (1978) Retrograde amnesia produced by post-trial injection of substance P into the substantia nigra. Brain Res 159:468–472
Huston JP, Stäubli U (1979) Post-trial injection of substance P into lateral hypothalamus and amygdala, respectively, facilitates and impairs learning. Behav Neural Biol 27:244–248
Huston JP, Stäubli U (1981) Substance P and its effects on learning and memory. In: Martinez JL, Jensen RA, Messing RB, Rigter H, McGaugh JL (eds) Endogenous peptides and learning and memory processes. Academic Press, New York, pp 521–540
Huston JP, Mueller CC, Mondadori C (1977) Memory facilitation by post-trial hypothalamic stimulation and other reinforcers: a central theory of reinforcement. Biobehav Rev 1:143–150
Iversen LL, Watson SP, Sandberg BE, Hunter J, Maggio J (1985) Biochemical pharmacology of substance P. In: Tsukada Y (ed) Perspectives on neuroscience. Springer, New York, pp 3–17
Kafetzopoulos E, Holzhäuer M-S, Huston JP (1986) Substance P injected into the region of the nucleus basalis magnocellularis facilitates performance of an inhibitory avoidance task. Psychopharmacology 90:281–283
Kastin AJ, Olson RD, Schally AV, Coy DH (1979) CNS effects of peripherally administered brain peptides. Life Sci 25:401–414
Koob FG (1987) Neuropeptides and memory. In: Iversen S, Iversen L, Snyder S (eds) Handbook of psychopharmacology, vol 19. Plenum Press, New York, pp 531–573
Lembeck F (1988) The 1988 Ulf von Euler Lecture. Acta Physiol Scand 133:435–454
Ljungdahl A, Hökfelt T, Nilsson G (1978) Distribution of substance P-like immunoreactivity in the central nervous system of the rat. — I. Cell bodies and nerve terminals. Neuroscience 3:861–894
Mazurek N, Pecht I, Teichberg VI, Blumberg S (1981) The role of the N-terminal tetrapeptide in the histamine releasing action of substance P. Neuropharmacology 20:1025–1027
Nagel JA, Huston JP (1988) Enhanced inhibitory avoidance learning produced by post-trial injections of substance P into the basal forebrain. Behav Neural Biol 49:374–385
Nicoll RA, Schenker C, Leeman SE (1980) Substance P as a transmitter candidate. Ann Rev Neurosci 3:227–268
Pelleymounter MA, Fisher Q, Schlesinger K, Hall M, Dearmey P, Stewart J (1986) The effect of substance P and its fragments on passive avoidance retention and brain monoamine activity. Behav Brain Res 21:119–127
Pelleymounter MA, Schlesinger K, Wehner J, Hall ME, Stewart JM (1988) Nigral 5-HT and substance P-induced enhancement of passive avoidance retention. Behav Brain Res 29:159–172
Pernow B (1983) Substance P. Pharmacol Rev 35:85–141
Reid M, Herrera-Marschitz M, Hökfelt T, Terenius L, Ungerstedt U (1988) Differential modulation of striatal dopamine release by intranigral injection ofγ-aminobutric acid (GABA), dynorphin A and substance P. Eur J Pharmacol 147:411–420
Sandberg BEB (1985) Structure-activity relationships for substance P: a review. In: Jordan CC, Oehme P (eds) Substance P: metabolism and biological action. Taylor & Francis, London, pp 65–81
Schlesinger K, Lipsitz DU, Peck PL, Pelleymounter MA, Stewart JM, Chase TN (1983a) Substance P enhancement of passive and active avoidance conditioning in mice. Pharmacol Biochem Behav 19:655–666
Schlesinger K, Lipsitz DU, Peck PL, Pelleymounter MA (1983b) Substance P reversal of electroconvulsive shock and cyclohexamide-induced retrograde amnesia. Behav Neural Biol 39:30–39
Schlesinger K, Pelleymounter MA, Van der Kamp J, Bader DL, Stewart JM, Chase TN (1986) Substance P facilitation of memory: effects in an appetitively motivated learning task. Behav Neural Biol 45:230–239
Spruijt BM, Gispen WH (1984) Behavioral sequences as an easy quantifiable parameter in experimental studies. Physiol Behav 32:707–710
Stäubli U, Huston JP (1985) Central action of substance P: possible role in reward. Behav Neural Biol 43:100–108
Stein L, Belluzzi JD (1979) Brain endorphins: possible role in reward and memory formation. Fed Proc 38:2468–2472
Stern P, Hadzovic J (1973) Pharmacological analysis of central actions of synthetic substance P. Arch Int Pharmacodyn 202:259–262
Tomaz C, Huston JP (1986) Facilitation of conditioned inhibitory avoidance by post-trial peripheral injection of substance P. Pharmacol Biochem Behav 25:469–472
Wetzel W, Matthies H (1982) Effect of substance P on the retention of a brightness discrimination task in rats. Acta Biol Med Germ 41:647–652
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Oitzl, M.S., Hasenöhrl, R.U. & Huston, J.P. Reinforcing effects of peripherally administered substance P and its C-terminal sequence pGlu6-SP6-11 in the rat. Psychopharmacology 100, 308–315 (1990). https://doi.org/10.1007/BF02244598
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02244598