Abstract
The acute effects of increasing doses of the antidepressant drugs amineptine (5–40 mg/kg, IP) and desipramine (5–20 mg/kg IP) were studied in mice on three parameters of the activity (the horizontal activity, the vertical activity and the number of small movements without displacement) measured in a computerized Digiscan actimeter. The horizontal and vertical activities were dose dependently and similarly increased by acute amineptine, whereas the number of movements without displacement was increased up to 10 mg/kg with no further significant modification up to 40 mg/kg; in contrast, all three parameters were reduced in an identical manner by desipramine. The changes in the responses to the selective D-1 dopamine (DA) receptor agonist SK&F 38393 (1.87–30 mg/kg, SC), to the selective D-2 DA receptor agonist LY 171555 (0.1–1.6 mg/kg, SC) and to the selective DA uptake inhibitor GBR 12783 (1.25–20 mg/kg, IP) were measured on the three parameters of activity in mice chronically treated with amineptine (20 mg/kg, IP twice daily during 15 days) or by desipramine (10 mg/kg, IP, twice daily during 15 days). The chronic treatments with amineptine or desipramine did not modify the motor stimulant effects GBR 12783 and of SK&F 38393 on the three parameters (excepted for a slight modification of the horizontal activity for 7.5 mg/kg SK&F 38393 in mice chronically treated with amineptine). In contrast, the motor inhibitory effects of the lowest doses of LY 171555 (0.1–0.4 mg/kg) were strongly reduced in mice chronically treated with amineptine or desipramine but only on the horizontal activity with no change on the vertical activity and on the number of small movements without displacement. These data indicate that, as in chronic treatment with typical antidepressant drugs like desipramine, chronic treatment with amineptine alters selectively the sedative effects induced by stimulation of D-2 DA autoreceptors in the mesolimbic dopaminergic area involved in the horizontal (locomotor) activity.
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References
Algeri S, Brunello N, Catto E, Mennini T, Ponzio F (1978) Biochemical effect of some new proposed antidepressant drugs on the monoaminergic system in rat brain. In: Garattini S (ed) Depressive disorders. Schattauer, Stuttgart, pp 155–168
Banerjee LP, Kung LS, Riggi ST, Chanda SK (1977) Development ofβ adrenergic receptor subsensitivity by antidepressants. Nature 268:455–457
Bonnet JJ, Costentin J (1986) GBR 12783, a potent and selective inhibitor of dopamine uptake: biochemical studies in vivo and ex vivo. Eur J Pharmacol 121:199–209
Bonnet JJ, Protais P, Chagraoui A, Costentin J (1986) High affinity [3H]-GBR 12783 binding to a specific site associated with the neuronal dopamine uptake complex in the central nervous system. Eur J Pharmacol 126:211–222
Bonnet JJ, Chagraoui A, Protais P, Costentin J (1987) Interactions of amineptine with the neuronal dopamine uptake system: neurochemical in vitro and in vivo studies. J Neural Transm 69:211–220
Brudzynski SM, Mogenson GJ (1985) Association of the mesolimbic locomotor region with locomotor activity induced by injections of amphetamine into the nucleus accumbens. Brain Res 334:77–85
Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Bunney WE (eds) Pre- and postsynaptic receptors. Dekker, New York, pp 49–65
Ceci A, Garattini S, Gobbi M, Mennini T (1986) Effect of long term amineptine treatment on pre- and postsynaptic mechanism in rat brain. Br J Pharmacol 88:269–275
Chagraoui A, Bonnet JJ, Protais P, Costentin J (1987) In vivo binding of [3H]-GBR 12783, a selective dopamine uptake inhibitor, in mouse striatum. Neurosci Lett 78:175–179
Charney DS, Menkes DB, Heninger GR (1981) Receptor sensitivity and the mechanism of action of antidepressant treatment. Implications for the etiology and therapy of depression. Arch Gen Psychiatry 38:1160–1180
Chiodo LA, Antelman SM (1980) Repeated tricyclics induce a progressive dopamine autoreceptor subsensitivity independent of daily drug treatment. Nature 287:451–453
Costall B, Naylor RJ (1976) A comparison of the abilities of typical neuroleptic agents and of thioridazine, clozapine, sulpiride and metoclopramide to antagonize the hyperactivity induced by dopamine applied intracerebrally to areas of the extrapyramidal and mesolimbic systems. Eur J Pharmacol 40:9–19
Crews FT, Smith CB (1978) Presynaptic alpha receptor subsensitivity after long-term antidepressant treatment. Science 202:322–324
Di Chiara G, Porceddu ML, Vargiu L, Argiolas A, Gessa GL (1976) Evidence for dopamine receptors mediating sedation in the mouse brain. Nature 264:564–566
Diggory GL, Buckett WR (1984) Chronic antidepressant administration fails to attenuate apomorphine — induced decreases in rat striatal dopamine metabolites. Eur J Pharmacol 105:257–263
Itoh Y, Goldman ME, Kebabian JW (1985) TL 333, a benzhydro/g/quinoline, stimulates both D-1 and D-2 dopamine receptors: implications for the selectivity of LY 141865 towards the D-2 receptor. Eur J Pharmacol 108:99–101
Karobath ME (1975) Tricyclic antidepressive drugs and dopamine sensitive adenylate cyclase from rat brain striatum. Eur J Pharmacol 30:159–163
Kelly PH, Seviour PW, Iversen SD (1975) Amphetamine and apomorphine responses in the rat following 6-OHDA lesions of the nucleus accumbens septi and corpus striatum. Brain Res 94:507–522
Klimek V, Nielsen M, Maj J (1985) Repeated treatment with imipramine decreased the number of 3H-piflutixol binding sites in the rat striatum. Eur J Pharmacol 109:131–132
Koller W, Herbster G, Anderson D, Wack R, Gordon J (1987) Quinpirole hydrochloride, a potential anti-parkinsonism drug. Neuropharmacology 26:1031–1036
Maggi A, U'Prichard DC, Enna SJ (1980) Differential effect of antidepressant treatment on brain monoaminergic receptors. Eur J Pharmacol 61:91–99
Maj J, Mogilnicka E, Klimek V (1979) The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists. J Neural Transm 44:221–228
Pijnenburg AJJ, Van Rossum JM (1973) Stimulation of locomotor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003–1005
Scavone C, Aizenstein ML, De Lucia R, Da Silva Planeta C (1986) Chronic imipramine administration reduces apomorphine inhibitory effects. Eur J Pharmacol 132:263–271
Serra G, Argiolas A, Klimek V, Fadda F, Gessa GL (1979) Chronic treatment with antidepressants prevent the inhibitory effect of small doses of apomorphine on dopamine synthesis and motor activity. Life Sci 25:415–420
Serra G, Argiolas A, Gessa GL (1981) Opposite changes in dopamine autoreceptors sensitivity induced by chronic antidepressants and neuroleptics. In: Apomorphine and other dopaminomimetics. Raven Press, New York, pp 133–138
Setler PE, Sarau HM, Zirckle CI, Saunders HJ (1978) The central effects of a novel dopamine agonist. Eur J Pharmacol 50:419–426
Simoni MG de, Toso GD, Algeri S, Ponzio F (1986) Differences in the effect of the antidepressant amineptine on striatal and limbic DOPAC measured by HPLC-ECD and in vivo voltametry. Eur J Pharmacol 123:433–439
Sugrue MF (1981) Chronic antidepressant administration and adaptative changes in central monoaminergic systems. In: Enna SJ, Malick JB, Richelson E (eds) Antidepressants: neurochemical, behavioral and clinical perspectives. Raven Press, New York, pp 13–30
Tsuruta K, Frey EA, Grewe CW, Cote TE, Eskey RL, Kebabian JW (1981) Evidence that LY 141865 specifically stimulates the D-2 dopamine receptor. Nature 292:463–465
Van der Zee P, Koger HS, Gootjes J, Hespe W (1980) Aryl 1,4-dialk(en)ylpiperazines as selective and very potent inhibitors of dopamine uptake. Eur J Med Chem 15:363–371
Vasse M, Chagraoui A, Protais P (1988) Climbing and stereotyped behaviours in mice require the stimulation of D-1 dopamine receptors. Eur J Pharmacol 148:221–229
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Chagraoui, A., Vasse, M. & Protais, P. Effects of chronic treatments with amineptine and despiramine on motor responses involving dopaminergic systems. Psychopharmacology 102, 201–206 (1990). https://doi.org/10.1007/BF02245922
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DOI: https://doi.org/10.1007/BF02245922