Abstract
The effects of different subcutaneous doses (0.08, 0.16, 0.31, 0.63 and 1.25 mg/kg) of apomorphine on self-stimulation in rats, with monopolar nichrome electrodes, implanted in the medial forebrain bundle at the level of the lateral hypothalamus were studied. Six different selected stimulus parameter combinations inducing different predictable response rates were used.
Apomorphine was found to produce a dose-related response stimulation and a dose-related response depression. The highest stimulation was obtained at 0.63 mg/kg, the highest depression at 1.25 mg/kg.
The response stimulation with apomorphine was 1. inversely related to the control response rate, i.e. the higher the control response rate, the lower the response stimulation after apomorphine and vice versa, 2. directly related to the control response rate of the individual rats, i.e. the highest response stimulation was obtained with the most sensitive rat and vice versa. The response inhibition with apomorphine was not related to the control response rates but was more pronounced during the first 1/2 h of the session.
It is postulated that
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1.
increased self-stimulation with apomorphine could be the result of an increased motor response output;
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2.
decreased self-stimulation with apomorphine could be due to non-adaptive behaviour as a result of non-physiological overexcitation with interruption of integrated behaviour;
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3.
a complex behavioural pattern like intracranial self-stimulation depends on different interacting systems, mediated by different transmitters.
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References
Amsler, C.: BeitrÄge zur Pharmakologie des Gehirns. Naunyn-Schmiedebergs Arch. exp. Path. Pharmak. 97, 1–14 (1923).
Andén, N. E., Fuxe, K., Hökfelt, T., Rubenson, A.: Evidence for dopamine receptor Stimulation by apomorphine. J. Pharm. Pharmacol. 19, 627–629 (1967).
Andén, N. E., Corrodi, H., Fuxe, K., Hökfelt, B., Rydin, C., Svensson, T.: Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci. 9, 513–523 (1970).
Andén, N. E., Buddard, P.: Influence of cholinergic mechanism on the function and turnover of brain dopamine. J. Pharm. Pharmacol. 23, 460–462 (1971).
Benešovà, G., Beneš, V.: Apomorphine and monoamines in the brain of rats. 12th Annual Psychopharmacological Conference Jesenik. Summary in Activ. nerv. sup. (Praha) 12, 3 (1970).
Berlyne, D. E.: Conflict, arousal and curiosity. New York: McGraw-Hill Book Comp. 1960.
Brizzee, K. R., Neal, L. M., Williams, P. M.: The chemoreceptor trigger zone for emesis in the monkey. Amer. J. Physiol. 180, 659–662 (1955).
Burkman, A. M., Tye, A., Nelson, J. W.: Antiemetics in the pigeon. J. Amer. pharm. Ass. 46, 140–144 (1957).
Butcher, L. L.: Effects of apomorphine on free-operant avoidance behavior in the rat. Europ. J. Pharmacol. 3, 163–166 (1968).
Butcher, L. L., Andén, N. E.: Effects of apomorphine and amphetamine on schedule-controlled behavior: reversal of tetrabenazine suppression and dopaminergic correlates. Europ. J. Pharmacol. 6, 255–264 (1969).
Corrodi, H., Fuxe, K., Lymgdahl, A., ögren, S. O.: Studies on the action of some psychoactive drugs on central noradrenaline neurons after inhibition of dopamine Β-hydroxylase. Brain Res. 24, 451–470 (1970).
Corrodi, H., Fuxe, K., Lidbrink, P.: Interaction between cholinergic and catecholaminergic neurones in the rat brain. Brain Res. 43, 397–416 (1972).
Costall, B., Naylor, R. J.: Modification of amphetamine effects by intracerebrally administered anticholinergic agents. Life Sci. 11 (I), 239–253 (1972).
Costall, B., Naylor, R. J., Olley, J. E.: On the involvement of the caudate-putamen, globus pallidus and substantia nigra with neuroleptic and cholinergic modifications of locomotor activity. Neuropsychopharmacol. 11, 317–330 (1972).
Dlabač, A.: Brain monoamines in antiapomorphine action of neuroleptics. IVth Int. Congr. Pharmacol. Basel, Abstract p. 67 (1969).
Ernst, A. M.: Relation between the action of dopamine and apomorphine on their O-methylated derivatives upon the CNS. Psychopharmacologia (Berl.) 7, 391–399 (1965).
Ernst, A., Smelik, P. G.: Site of action of dopamine and apomorphine on compulsive gnawing behavior of rats. Experientia (Basel) 22, 837–839 (1966).
Goldstein, M., Freedman, L. S., Backstrom, T.: The inhibition of catecholamine biosynthesis by apomorphine. J. Pharm. Pharmacol. 22, 715–717 (1970).
Isaacs, B., Mc Arthur, J. G.: Influence of chlorpromazine and promethazine on vomiting induced with apomorphine in man. Lancet 1954 II, 570–572.
Janssen, P. A. J., Niemegeers, C. E. J., Jageneau, A. H. M.: Apomorphine-antagonism in rats. Arzneimittel-Forsch. 10, 1003–1005 (1960).
Koster, R.: Comparative studies of emesis in pigeons and dogs. J. Pharmacol. exp. Ther. 119, 406–417 (1957).
Maj, J., Grabowska, M., Mogilnicka, E.: Effect of dopa on brain CA and on locomotor activity. VIIth CINP Congress, Prague, Abstract p. 286, 1970.
Mitchell, L.: Dimenhydrinate vs diphenhydramine. Science 112, 154 (1959).
Mucačevic, G., Stötzer, H., Wick, H.: Pharmakologische Eigenschaften des Antihistaminicums 1-Dimethyl amino-aethyl-2-α-pyridyl-4-oxo-1,2,3,4-tetrahydrochinazolin. Arzneimittel-Forsch. 15, 613–618 (1965).
Niemegeers, C. J. E.: The apomorphine antagonism test in dogs. Pharmacology 6, 353–364 (1971).
NybÄck, A., Schubert, J., Sedvall, G.: Effects of apomorphine and pimozide on synthesis and turnover of labelled catecholamines in mouse brain. J. Pharm. Pharmacol. 22, 622–624 (1970).
Nymark, M.: Apomorphine provoked stereotypy in the dog. Psychopharmacologia (Berl.) 26, 361–368 (1972).
Oliveira, L. De, Graeif, F. G.: Comparison between the effects of apomorphine and amphetamine on operant behavior. Europ. J. Pharmacol. 18, 159–165 (1972).
Rotrosen, J., Wallach, M. B., Angrist, B. M., Gershon, S.: Antagonism of apomorphine induced stereotypy and emesis in dogs by thioridazine, haloperidol and pimozide. Psychopharmacologia (Berl.) 26, 185–194 (1972).
Schields, G. K., Ballinger, G. M., Hathaway, B. N.: Antiemetic effectiveness of haloperidol in human volunteers challenged with apomorphine. Curr. Res. 50, 1017–1024 (1971).
Senault, B.: Syndrome agressif induit par l'apomorphine chez le rat. J. Physiol. (Paris) 60, suppl. 2, 543–544 (1968).
Strömberg, U., Svensson, T. H.: L-dopa induced effects on motor activity in mice after inhibition of dopamine-Β-hydroxylase. Psychopharmacologia (Berl.) 19, 53–60 (1971).
Svensson, T. H., Waldeck, B.: On the role of brain catecholamines in motor activity: experiments with inhibition of synthesis and of monoamine oxidase. Psychopharmacologia (Berl.) 18, 357–365 (1970).
Ther, L., Schramm, H.: Apomorphinsynergismus (Zwangsnagen bei MÄusen) als Test zur Differenzierung psychotroper Substanzen. Arch. int. Pharmacodyn. 138, 302–310 (1962).
Thomas, J.: Hyperkinetic syndromes in the rat; the mode of action of amphetamine and apomorphine. Fed. Proc. 29, 1488 (1972).
Ungerstedt, U, Butcher, L. L., Butcher, S. G., Andén, N. E., Fuxe, K.: Direct chemical stimulation of dopaminergic mechanism in the neostriatum of the rat. Brain Res. 14, 461–471 (1969).
Van Rossum, J. M.: Antagonism by neuroleptics of abnormal behavior induced by activation of brain dopamine receptors. In: The Neuroleptics, pp. 65–70 (Eds. D. P. Bobon, P. A. J. Janssen and J. Bobon). Basel: Karger 1970.
Wauquier, A., Niemegeers, C. J. E., Geivers, H. A.: Intracranial self-stimulation in rats as a function of various stimulus parameters. I. An empirical study with monopolar electrodes in the medial forebrain bundle. Psychopharmacologia (Berl.) 23, 238–260 (1972).
Wauquier, A., Niemegeers, C. J. E.: Intracranial self-stimulation in rats as a function of various stimulus parameters. II. Influence of haloperidol, pimozide and pipamperone on medial forebrain stimulation with monopolar electrodes. Psychopharmacologia (Berl.) 27, 191–202 (1972).
Weissman, A.: Apomorphine elicitation of key pecking in a pigeon. Arch. int. Pharmacodyn. 160, 330–332 (1966).
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Wauquier, A., Niemegeers, C.J.E. Intracranial self-stimulation in rats as a function of various stimulus parameters. Psychopharmacologia 30, 163–172 (1973). https://doi.org/10.1007/BF00421431
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DOI: https://doi.org/10.1007/BF00421431