Abstract
In general, preweanling and adult rats respond similarly when challenged with competitive dopamine (DA) agonists or antagonists. In contrast, results using a noncompetitive antagonist suggest that the D1 and D2 receptor systems of preweanling and adult rats differ in some critical way. To further assess this phenomenon, the behavioral effects of irreversible receptor blockade were assessed across 8 days in NPA (a nonselective DA agonist), quinpirole (a D2 agonist), or SKF 38393 (a D1 agonist) treated 17-day-old rat pups. The irreversible antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) did not block the locomotor activity and rearing of NPA- or quinpirole-treated rat pups, nor did EEDQ reduce SKF 38393-induced grooming. Moreover, pretreatment with EEDQ appeared to potentiate the normal increases in locomotor activity and rearing produced by NPA, but only when D2 receptors were not protected by a previous injection of sulpiride (a D2 antagonist). Taken together, these results are consistent with the presence of large reserves of D1 and D2 receptors in the preweanling rat pup.
Similar content being viewed by others
References
Arnt J (1987) Behavioral studies of dopamine receptors: evidence for regional selectivity and receptor multiplicity. In: Creese I, Fraser CM (eds) Receptor biochemistry and methodology, vol 8. Dopamine receptors. Liss, New York, pp 199–231
Arnt J, Hyttel J (1989) Selective inactivation of dopamine D1 and D2 receptors in 6-hydroxydopamine-lesioned rats: evidence that the effect of D1 and D2 agonists can be expressed in the absence of the heterologous DA receptor. Pharmacol Toxicol 64:116–119
Arnt J, Hyttel J, Perregaard J (1987) Dopamine D-1 receptor agonist combined with the selective D-2 agonist quinpirole facilitate the expression of oral stereotyped behaviour in rats. Eur J Pharmacol 133:137–145
Arnt J, Hyttel J, Meier E (1988) Inactivation of dopamine D-1 or D-2 receptors differentially inhibits stereotypies induced by dopamine agonists in rats. Eur J Pharmacol 155:37–47
Barone P, Davis TA, Braun AR, Chase TN (1986) Dopaminergic mechanisms and motor function: characterization of D-1 and D-2 receptor interactions. Eur J Pharmacol 123:109–114
Bordi F, Meller E (1989) Enhanced behavioral stereotypies elicited by intrastriatal injections of D1 and D2 dopamine agonists in intact rats. Brain Res 504:276–283
Bordi F, Carr KD, Meller E (1989) Stereotypies elicited by injection of N-propylnorapomorphine into striatal subregions and nucleus accumbens. Brain Res 489:205–215
Braun AR, Chase TN (1986) Obligatory D-1/D-2 receptor interaction in the generation of dopamine agonist related behaviors. Eur J Pharmacol 131:301–306
Cameron DL, Crocker AD (1988) Alkylation of striatal dopamine receptors abolishes stereotyped behavior but has no effect on dopamine adenylate cyclase activity. Neurosci Lett 90:165–171
Cameron DL, Crocker AD (1989) Localization of striatal dopamine receptor function by central injection of an irreversible receptor antagonist. Neuroscience 32:81–85
Clark D, White FJ (1987) Review: D1 dopamine receptor the search for a function: a critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1:347–388
Crawford CA, Rowlett JK, McDougall SA, Elkins N, Bardo MT (1991) Developmental differences in D1 and D2 dopamine receptor depletion and turnover in rats after irreversible antagonist treatment. Soc Neurosci Abstr 17:1350
Crawford CA, McDougall SA, Rowlett JK, Bardo MT (1992) Depletion of dopamine binding sites and dopamine levels and changes in dihydroxyphenylacetic acid levels in the 17- and 90-day-old rat striatum after irreversible receptor antagonism. Neurosci Lett 137:265–269
Dall'Olio R, Gandolfi O, Vaccheri A, Roncada P, Montanaro N (1988) Changes in the behavioral responses to the combined administration of D1 and D2 dopamine agonists in normosensitive and D1 supersensitive rats. Psychopharmacology 95:381–385
Davis A, Jenner P, Marsden CD (1990) Differential ability of selective and non-selective dopamine agonists to induce climbing in the rat indicates the involvement of both D-1 and D-2 receptors in this behavior. Psychopharmacology 100:19–26
Double KL, Crocker AD (1990) Effects of inactivation of D1 dopamine receptors on stereotypic and thermic responses to quinpirole (LY 171555). Neurosci Lett 115:81–85
Eilam D, Talangbayan H, Canaran G, Szechtman H (1992) Dopaminergic control of locomotion, mouthing, snout contact, and grooming: opposing roles of D1 and D2 receptors. Psychopharmacology 106:447–454
Gandolfi O, Dall'Olio R, Vaccheri A, Roncada P, Montanaro N (1988) Responses to selective D-1 and D-2 agonists after repeated treatment with D-1 and D-2 antagonists. Pharmacol Biochem Behav 30:463–469
Gelbard HA, Teicher MH, Faedda G, Baldessarini RJ (1989) Postnatal development of dopamine D1 and D2 receptor sites in rat striatum. Brain Res 49:123–130
Giorgi O, Biggio G (1990a) Unilateral inactivation of dopamine receptors after intrastriatal injection of N-ethoxy-carbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ): a novel rotational model to investigate dopamine receptor interactions. Pharmacol Biochem Behav 35:877–884
Giorgi O, Biggio G (1990b) Selective unilateral inactivation of striatal D1 and D2 dopamine receptor subtypes by EEDQ: turning behavior elicited by D2 dopamine receptor agonists. Brain Res 533:53–59
Giorgi O, De Montis G, Porceddu ML, Mele S, Calderini G, Toffano G, Biggio G (1987) Developmental and age-related changes in D1-dopamine receptors and dopamine content in the rat striatum. Dev Brain Res 35:283–290
Hamblin MW, Creese I (1983) Behavioral and radioligand binding evidence for irreversible dopamine receptor blockade by N-ethoxycarbonyl-2-ethoxy-1, 2-dihydroquinoline. Life Sci 32:2247–2255
Kolta MG, Scalzo FM, Ali SF, Holson RR (1990) Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats. Psychopharmacology 100:377–382
Kula NS, George T, Baldessarini RJ (1992) Rate of recovery of D1 and D2 dopaminergic receptors in young vs. adult rat striatal tissue following alkylation with ethoxycarbonyl-ethoxy-dihydroquinoline (EEDQ). Dev Brain Res 66:286–289
Leff SE, Gariano R, Creese I (1984) Dopamine receptor turnover rates in rat striatum are age-dependent. Proc Natl Acad Sci USA 81:3910–3914
Longoni R, Spina L, Di Chiara G (1987a) Permissive role of D-1 receptor stimulation for the expression of D-2-mediated behavioural responses. Yawning in rats. Eur J Pharmacol 134:163–173
Longoni R, Spina L, Di Chiari G (1987b) Permissive role of D-1 receptor stimulation for the expression of D-2 mediated behavioral responses: a quantitative phenomenological study in rats. Life Sci 42:2135–2145
Mashurano M, Waddington JL (1986) Stereotyped behaviour in response to the selective D-2 dopamine receptor agonist RU 24213 is enhanced by pretreatment with the selective D-1 agonist SK&F 38393. Neuropharmacology 25:947–949
McDougall SA, Arnold TF, Nonneman AJ (1990) Ontogeny of locomotor activity and grooming in the young rat: role of D1 and D2 receptors. Eur J Pharmacol 186:223–230
McDougall SA, Crawford CA, Nonneman AJ (1992) Effects of irreversible dopamine receptor inactivation on locomotor activity and grooming in the 17- and 90-day-old rat. Psychopharmacology 106:502–510
Meller E, Bohmaker K, Namba Y, Friedhoff AJ, Goldstein M (1987) Relationship between receptor occupancy and response at striatal autoreceptors. Mol Pharmacol 31:592–598
Meller E, Enz A, Goldstein M (1988) Absence of receptor reserve at striatal dopamine receptors regulating cholinergic neuronal activity. Eur J Pharmacol 155:151–154
Meller E, Bordi F, Bohmaker K (1989a) Behavioral recovery after irreversible inactivation of D-1 and D-2 dopamine receptors. Life Sci 44:1019–1026
Meller E, Hizami R, Kreuter L (1989b) Hypothermia in mice: D2 dopamine receptor mediation and absence of spare receptors. Pharmacol Biochem Behav 32:141–145
Molloy AG, Waddington JL (1984) Dopaminergic behaviour stereospecifically promoted by the D-1 agonist R-SK&F 38393 and selectively blocked by the D-1 antagonist SCH 23390. Psychopharmacology 82:409–410
Moody CA, Spear LP (1992) Ontogenetic differences in the psychopharmacological responses to separate and combined stimulation of D1 and D2 dopamine receptors during the neonatal to weanling age period. Psychopharmacology 106:161–168
Murray AM, Waddington JL (1989) The induction of grooming and vacuous chewing by a series of selective D-1 dopamine receptor agonists: two directions of D-1:D-2 interaction. Eur J Pharmacol 160:377–384
Murrin LC, Zeng W (1986) Postnatal ontogeny of D2 receptors in rat striatum. Biochem Pharmacol 35:1159–1162
Murrin LC, Zeng W (1990) Ontogeny of dopamine D1 receptors in forebrain: a quantitative autoradiographic study. Dev Brain Res 57:7–13
Pugh MT, O'Boyle KM, Molloy AG, Waddington JL (1985) Effects of the putative D-1 antagonist SCH 23390 on stereotyped behavior induced by the D-2 antagonist RU24213. Psychopharmacology 87:308–312
Rosengarten H, Schweitzer JW, Friedhoff AJ (1989) A full repetitive jaw movement response after 70% depletion of caudate D1 receptors. Pharmacol Biochem Behav 34:895–897
Serra G, Collu M, Gessa GL (1987) Yawning is elicited by D2 dopamine agonists but is blocked by the D1 antagonist, SCH 23390. Psychopharmacology 91:330–333
Waddington JL (1989) Functional interactions between D1 and D2 dopamine receptor systems: their role in the regulation of psychomotor behavior, putative mechanisms, and clinical relevance. J Psychopharmacol 3:54–63
White FJ, Bednarz LM, Wachtel SR, Hjorth S, Brooderson RJ (1988) Is stimulation of both D1 and D2 receptors necessary for the expression of dopamine-mediated behaviors? Pharmacol Biochem Behav 30:189–193
Yokoo H, Goldstein M, Meller E (1988) Receptor reserve at striatal dopamine receptors modulating the release of [3H] dopamine. Eur J Pharmacol 155:323–327
Zeng W, Hyttel J, Murrin LC (1988) Ontogeny of dopamine D1 receptors in rat striatum. J Neurochem 50:862–867
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
McDougall, S.A., Crawford, C.A. & Nonneman, A.J. Behavioral effects of selective and nonselective dopamine agonists on young rats after irreversible antagonism of D1 and/or D2 receptors. Psychopharmacology 111, 225–232 (1993). https://doi.org/10.1007/BF02245528
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245528