Abstract
Various drugs acting on brain serotonin or catecholamines were administered concurrently with morphine during the development of dependence or before naloxoneprecipitated withdrawal syndrome. Of the various drugs only cyproheptadine, a serotonin antagonist, and piribedil, a dopamine agonist, reduced the frequency of jumping (but not of diarrhea or ptosis) when administered with morphine during development of dependence. When administered before naloxone, d-fenfluramine, a serotonin releaser, markedly reduced jumping, but not diarrhea and ptosis, and clonidine blocked these latter signs without affecting the frequency of jumping. Of the other drugs examined only phenoxybenzamine reduced diarrhea in morphine-abstinent rats. It is suggested that serotonin is involved in the mechanisms which lead to compulsive jumping during naloxoneprecipitated withdrawal, whereas adrenergic sites on which clonidine acts are mainly involved in the expression of signs, such as ptosis and diarrhea. No clear evidence was obtained of a role for dopamine in the withdrawal signs studied.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén NE, Strömbom U (1974) Adrenergic receptor blocking agents: Effects on central noradrenaline and dopamine receptors and on motor activity. Psychopharmacologia 38:91–103
Andén NE, Corrodi H, Fuxe K, Hokfelt B, Hokfelt T, Rydin C, Svensson T (1970) Evidence for a central noradrenaline receptor stimulation by clonidine. Life Sci 9:513–523
Andén NE, Gomes C, Persson B, Trolin G (1978) R 28935 and prazosin: Effects on central and peripheral alpha-adrenoreceptor activity and on blood pressure. Naunyn-Schmiedebergs Arch Pharmacol 302:299–306
Ary M, Cox B, Lomax P (1977) Dopaminergic mechanisms in precipitated withdrawal in morphine-dependent rats. J Pharmacol Exp Ther 200:271–276
Bedard P, Pycock CJ (1977) Wet-dog shake behaviour in the rat: A possible quantitative model of central 5-hydroxytryptamine activity. Neuropharmacology 16:663–670
Bläsig J, Herz A, Reinhold K, Zieglgänsberger S (1973) Development of physical dependence on morphine in respect to time and dosage and quantification of the precipitated withdrawal syndrome in rats. Psychopharmacologia 33:19–38
Bolme P, Corrodi H, Fuxe K, Hokfelt T, Lidbrink P, Goldstein M (1974) Possible involvement of central adrenaline neurons in vasomotor and respiratory control. Studies with clonidine and its interactions with piperoxane and yohimbine. Eur J Pharmacol 28:89–94
Braestrup C (1974) Effects of phenoxybenzamine, aceperone and clonidine on the level of 3-methoxy-4-hydroxyphenyglycol (MOPEG) in rat brain. J Pharm Pharmacol 26:139–141
Cedarbaum JM, Aghajanian GK (1976) Noradrenergic neurons of the locus coeruleus: Inhibition by epinephrine and activation by the α-antagonist piperoxane. Brain Res 112:413–419
Cheney DL, Goldstein A (1971) The effect of p-chlorophenylalanine on opiate-induced running, analgesia, tolerance and physical dependence in mice. J Pharmacol Exp Ther 177:309–315
Clineschmidt BV, Lotti JV (1974) Indoleamine antagonists: Relative potencies as inhibitors of tryptamine- and 5-hydroxytryptophancvoked responses. Br J Pharmacol 50:311–313
Consolo S, Fanelli R, Garattini S, Ghezzi D, Jori A, Ladinsky H, Marc V, Samanin R (1975) Dopaminergic-cholinergic interaction in the striatum: Studies with piribedil. Adv Neurol 9:257–272
Cools AR, Van Rossum JM (1976) Excitation-mediating and inhibition mediating dopamine-receptors: A new concept towards a better understanding of electrophysiological, biochemical, pharmacological, functional and clinical data. Psychopharmacologia 45:243–254
Cowan A, Macfarlane IR (1975) Effect of propranolol on antinociceptive, tolerance- and dependence-producing properties of morphine in rodents and monkeys. Eur J Pharmacol 34:87–94
Fuller RW, Snoddy HD (1977) Biphasic effects of m-chlorophenylpiperazine on 3,4-dihydroxyphenylacetic acid concentration in rat brain. Res Commun Chem Pathol Pharmacol 17:551–554
Garattini S, Buczko W, Jori A, Samanin R (1975a) On the mechanism of action of fenfluramine. Postgrad Med J 51 (Suppl 1):27–35
Garattini S, Fanelli R, Jori A, Consolo S, Ladinsky H, Samanin R (1975b) Pharmacological and biochemical studies on piribedil (ET495). In: First International Symposium on Piribedil. Servier Research Institute, Paris, pp 240–244
Gianutsos G, Hynes MD, Puri SK, Drawbaugh RB, Lal H (1974) Effect of apomorphine and nigrostriatal lesions on aggression and striatal dopamine turnover during morphine withdrawal: Evidence for dopaminergic supersensitivity in protracted abstinence. Psychopharmacologia 34:37–44
Grabowska M, Antkiewicz L, Michaluk J (1974) A possible interaction of quipazine with central dopamine structures. J Pharm Pharmacol 26:74–76
Haubrich DR, Blake DE (1973) Modification of serotonin metabolism in rat brain after acute or chronic administration of morphine. Biochem Pharmacol 22:2753–2759
Herz A, Bläsig J, Papeschi R (1974) Role of catecholaminergic mechanisms in the expression of the morphine abstinence syndrome in rats. Psychopharmacologia 39:121–143
Ho IK, Brase DA, Loh HH, Way EL (1975) Influence of l-tryptophan on morphine analgesia, tolerance and physical dependence. J Pharmacol Exp Ther 193:35–43
Ho IK, Loh HH, Way EL (1973) Influence of 5,6-dihydroxytryptamine on morphine tolerance and physical dependence. Eur J Pharmacol 21:331–336
Ho IK, Lu SE, Stolman S, Loh HH, Way EL (1972) Influence of p-chlorophenylalanine on morphine tolerance and physical dependence and regional brain serotonin turnover studies in morphinetolerant dependent mice. J Pharmacol Exp Ther 182:155–165
Hoffman BB, De Lean A, Wood CL, Schocken DD, Lefkowitz RJ (1979) Alpha-adrenergic receptor subtypes: Quantitative assessment by ligand binding. Life Sci 24:1739–1746
Iwamoto ET, Loh HH, Way EL (1976) Circling behavior after narcotic drugs and during naloxone-precipitated abstinence in rats with unilateral nigral lesions. J Pharmacol Exp Ther 197:503–516
Janssen PAJ, Van Bever WFM (1977) Butyrophenones and diphenylbutylamines. In: Usdin E, Forrest IS (eds) Psychotherapeutic drugs, pt II, applications. Marcel Dekker, New York, p 869–921
Jhamandas K, Sutak M, Bell S (1973) Modification of precipitated morphine withdrawal syndrome by drugs affecting cholinergic mechanisms. Eur J Pharmacol 24:296–305
Lemberger L, Witt ED, Davis JM, Kopin IJ (1970) The effects of haloperidol and chlorpromazine on amphetamine metabolism and amphetamine stereotype behavior in the rat. J Pharmacol Exp Ther 174:428–433
Marshall I, Grahame-Smith DG (1971) Evidence against a role of brain 5-hydroxytryptamine in the development of physical dependence upon morphine in mice. J Pharmacol Exp Ther 173:634–641
Martin WR, Eades CG, Thompson WO, Thompson JA, Flanary HG (1974) Morphine physical dependence in the dog. J Pharmacol Exp Ther 189:759–771
Meyer DR, Sparber SB (1976) Clonidine antagonizes body weight loss and other symptoms used to measure withdrawal in morphinepelleted rats given naloxone. Pharmacologist 18:236
Miranda F, Invernizzi R, Samanin R (1979) Studies on the mechanism of the interaction of narcotic analgesics with brain serotonin. Pharmacol Res Commun 11:455–465
Samanin R, Miranda F, Mennini T (1978) Serotonergic mechanismis of narcotic action. In: Adler ML, Manara L, Samanin R (eds) Factors affecting the action of narcotics. Raven Press, New York, pp 523–541
Samanin R, Cervo L, Rochat C (1980a) Changes of physical morphine dependence in rats chronically treated with drugs acting on brain 5-hydroxytryptamine. J Pharm Pharmacol 32:150
Samanin R, Cervo L, Rochat C, Poggesi E, Mennini T (1980b) Reduction in the number of serotonin receptors in the brain stem of morphine dependent rats: Relation to blockade of naloxoneprecipitated jumping by serotonin agonists. Life Sci 27:1141–1146
Samanin R, Mennini T, Ferraris A, Bendotti C, Borsini F (1980c) Hyperand hyposensitivity of central serotonin receptors: 3H-Serotonin binding and functional studies in the rat. Brain Res 189:449–457
Spano PF, Biggio G, Casu M, Gessa GL, Bareggi SR, Govoni S, Trabucchi M (1978) Interaction of metergoline with striatal dopamine system. Life Sci 23:2383–2392
Svensson TH, Bunney BS, Aghajanian GK (1975) Inhibition of both noradrenergic and serotonergic neurons in brain by the α-adrenergic agonist clonidine. Brain Res 92:291–306
Takemori AE, Sprague GL (1978) Comparison of naloxone-induced platform vertical jumping in the assessment of physical dependence in morphine-dependent mice. J Pharm Pharmacol 30:585–586
Way EL, Loh HH, Shen FH (1968) Morphine tolerance, physical dependence, and synthesis of brain 5-hydroxytryptamine. Science 162:1290–1292
Way EL, Loh HH, Shen FH (1969) Simultaneous quantitative assessment of morphine tolerance and physical dependence. J Pharmacol Exp Ther 167:1–8
Wolfe BB, Harden TK, Sporn JR, Molinoff PB (1978) Presynaptic modulation of beta-adrenergic receptors in rat cerebral cortex after treatment with antidepressants. J Pharmacol Exp Ther 207:446–457
Yarbrough GG, Buxbaum DM, Sanders-Bush E (1973) Biogenic amines and narcotic effects. II. Serotonin turnover in the rat after acute and chronic morphine administration. J Pharmacol Exp Ther 185:328–335
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Cervo, L., Rochat, C., Romandini, S. et al. Evidence of a preferential role of brain serotonin in the mechanisms leading to naloxone-precipitated compulsive jumping in morphine-dependent rats. Psychopharmacology 74, 271–274 (1981). https://doi.org/10.1007/BF00427109
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00427109