Abstract
One major mechanism underlying the central action of neurotensin is an interaction with the function of dopamine (DA)-containing neurons. In addition, direct or indirect DA agonists have been reported to promote neurotensin release. We have found that SR 48692, a non-peptide neurotensin receptor antagonist (0.04 – 0.64 mg/kg orally), antagonizes (50–65%) yawning induced by apomorphine (0.07 mg/kg SC) or bromocriptine (2 mg/kg IP) in rats, and turning behaviour induced by intrastriatal injection of apomorphine (0.25 µg), (+) SKF 38393 (0.1 µg), bromocriptine (0.01 ng) or (+) amphetamine (10 µg) in mice. Other apomorphine-induced effects in mice and rats such as climbing, hypothermia, hypo- and hyper-locomotion, penile erections and stereotypies were not significantly modified by SR 48692. Taken together, these data suggest that neurotensin may play a permissive role in the expression of some but not all behavioural responses to DA receptor stimulation.
Similar content being viewed by others
References
Al-Rhodan NRF, Richelson E, Gilbert JA, Mc Cormick DJ, Kanba KS, Pfenning MA, Larson EW, Yaksh TL (1991) Structure-antinociceptive activity of neurotensin and some novel analogues in the periaqueductal gray region of the brainstem. Brain Res 557:227–235
Bean AJ, During MJ, Roth RH (1990) Effects of dopamine autoreceptor stimulation on the release of colocalized transmitters: in vivo release of dopamine and neurotensin from rat prefrontal cortex. Neurosci Lett 108:143–148
Dourish CT, Hutson PH (1985) Bilateral lesions of the striatum induced with 6-hydroxydopamine abolish apomorphine-induced yawning in rats. Neuropharmacology 24:1051–1055
During MJ, Bean AJ, Roth RH (1992) Effects of CNS stimulants on the in vivo release of the colocalized transmitters, dopamine and neurotensin, from rat prefrontal cortex. Neurosci Lett 140:129–133
Fuxe K, O'Connor WT, Antonelli T, Osborne PG, Tanganelli S, Agnati LF, Ungerstedt U (1992) Evidence for a substrate of neuronal plasticity based on pre- and postsynaptic neurotensin-dopamine receptor interactions in the neostriatum. Proc Natl Acad Sci 89:5591–5595
Gully D, Canton M, Boigegrain R, Jeanjean F, Molimard JC, Poncelet M, Gueudet C, Heaulme M, Leyris R, Brouard A, Pelaprat D, Labbé-Jullié C, Mazella J, Soubrié P, Maffrand JP, Rostène W, Kitabgi P, Le Fur G (1993) Biochemical and pharmacological profile of a potent and selective nonpeptide antagonist of the neurotensin receptor. Proc Natl Acad Sci 90:65–69
Jolicoeur FB, Gagne MA, Rivest R, Drumheller A, St-Pierre S (1991) Neurotensin selectively antagonizes apomorphine-induced stereotyped climbing. Pharmacol Biochem Behav 38:463–465
Kalivas P W (1993) Neurotransmitter regulation of dopamine neurons in the ventral tegmental area. Brain Res Rev 18:75–113
Merchant KM, Gibb JW, Hanson G.R. (1989) Role of dopamine D-1 and D-2 receptors in the regulation of neurotensin systems of the neostriatum and the nucleus accumbens. Eur J Pharmacol 160:409–412
Merchant KM, Bush LG, Gibb JW, Hanson GR (1990) Neurotensin-dopamine interactions in the substantia nigra of the rat brain. J Pharmacol Exp Ther 255:775–790
Morelli M, Longoni R, Spina L, Di Chiara G (1986) Antagonism of apomorphine-induced yawning by SCH 23390: evidence against the autoreceptor hypothesis. Psychopharmacology 89:259–260
Nemeroff CB, Luttinger D, Hernandez DE, Mailman RB, Mason GA, Davis GA, Widerlöv E, Frye GD, Kilts CA, Beaumont K, Breese GR, Prange AJ JR (1983) Interactions of neurotensin with brain dopamine systems: biochemical and behavioural studies. J Pharmacol Exp Ther 225:337–345
Nouel D, Costentin J (1991) Inhibition of apomorphine-induced yawning and penile erection by neurotensin. Peptides 12:755–759
Poncelet M, Santucci V, Paul R, Gueudet C, Lavastre S, Guitard J, Steinberg R, Terranova JP, Brelière JC, Soubrié P, Le Fur G (1993) Neuropharmacological profile of a novel and selective ligand of the sigma site: SR 31742A. Neuropharmacology 32:605–615
Poncelet M, Gueudet C, Gully D, Soubrié P, Le Fur G (1994) Turning behaviour induced by intrastriatal injection of neurotensin in mice: sensitivity to non-peptide neurotensin antagonists. Naunyn-Schmiedeberg's Arch Pharmacol 349:57–60
Puech AJ, Simon P, Boissier JR (1978) Benzamides and classical neuroleptics: comparison of their actions using 6 apomorphine-induced effects. Eur J Pharmacol 50:291–300
Rivest R, Jolicoeur FB, Marsden CA (1991) Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo. Neuropharmacology 30:25–33
Sanz B, Exposito I, Mora F (1993) Effects of neurotensin on the release of glutamic acid in the prefrontal cortex and striatum of the rat. NeuroReport 4:1194–1196
Seutin V, Massotte L, Dresse A (1989) Electrophysiological effects of neurotensin on dopaminergic neurones of the ventral tegmental area of the rat in vitro. Neuropharmacology 28:949–954
Singh NA, Bush LG, Gibb JW, Hanson GR (1990) Dopamine-mediated changes in central nervous system neurotensin systems: a role for NMDA receptors. Eur J Pharmacol 187:337–344
Steinberg R, Bougault I, Souilhac J, Gully D, Le Fur G, Soubrié P (1994) Blockade of neurotensin receptors by the antagonist SR 48692 partially prevents retrograde axonal transport of neurotensin in rat nigrostriatal system. Neurosci Letter 166:106–108
Stoessel AJ, Dourish CT, Iversen SD (1987) Apomorphine-induced yawning in rats is abolished by bilateral 6-hydroxydopamine lesions of the substantia nigra. Psychopharmacology 93:336–342
Tanganelli S, Von Euler G, Fuxe K, Agnati LF, Ungerstedt U (1989) Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum. Brain Res 502:319–324
Ushijima I, Yamada K, Inoue T, Tokunaga T, Furukawa T, Noda Y (1984) Muscarinic and nicotinic effects on yawning and tongue protruding in the rat. Pharmacol Biochem Behav 21:297–300
Waddington JL, O'Boyle K.M. (1989) Drugs acting on brain dopamine receptors: a conceptual re-evaluation five years after the first selective D-1 antagonist. Pharmacol Ther 43:1–52
Worms P, Gueudet C, Biziere K (1986) Induction of turning by direct intrastriatal injection of dopaminomimetic drugs in mice: pharmacological analysis of a simple screening model. Life Sci 39:2199–2208
Zarrindast MR, Jamshidzadeh A (1992) Inhibitory effect of morphine on yawning induced by cholinoceptor and dopamine D2 receptor activation in rats. Br J Pharmacol 105:675–678
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Poncelet, M., Souilhac, J., Gueudet, C. et al. Effects of SR 48692, a selective non-peptide neurotensin receptor antagonist, on two dopamine-dependent behavioural responses in mice and rats. Psychopharmacology 116, 237–241 (1994). https://doi.org/10.1007/BF02245067
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245067