Abstract
The effect of cocaine (20 mg/kg SC) on presynaptic mechanisms of release for dopamine (DA) and for serotonin (5-HT) was studied in nucleus accumbens of unrestrained rats (Rattus norvegicus). The studies were done by assaying synaptic concentrations of DA and 5-HT in the presence of the neuronal impulse flow inhibitor, γ-butyrolactone (γ-BL). The results were compared with cocaine effects on accumbens DA and 5-HT in the freely moving rat, without γ-BL treatment. A neurochemical time course profile showed that the cocaine-induced increase in accumbens synaptic concentrations of DA was significantly blocked (p<0.0001) after DA impulse flow was significantly inhibited (p<0.0038) by γ-BL (35.8%). The neurochemical time course profile concurrently showed that the cocaine-induced decrease in accumbens synaptic concentrations of 5-HT was significantly blocked (p<0.0004) after impulse flow was significantly inhibited (p<0.025) by γ-BL (50.6%). The findings show that cocaine's effects on synaptic concentrations for DA and for HT in accumbens are dependent on neuronal impulse flow. The findings indicate that presynaptic releasing mechanisms, which may be different for DA vis-à-vis 5-HT, play a role in the mechanism of action of cocaine.
Keywords: Cocaine, Gamma-butyrolactone (γ-BL), Dopamine, Serotonin, Nucleus accumbens, Freely moving rat, In vivo electrochemistry (voltammetry), Presynaptic release
References
- 1.Aghajanian G.K., Roth R.H. Gamma-hydroxybutyrate-induced increase in brain dopamine: localization by fluorescence microscopy. J. Pharmacol. Exp. Ther. 1970;175:131–138. [PubMed] [Google Scholar]
- Aigner T.G., Balster R.L. Choice behavior in rhesus monkeys: Cocaine versus food. Science. 1978;201:534–535. doi: 10.1126/science.96531. [DOI] [PubMed] [Google Scholar]
- 2.Blaha C.D., Coury A., Fibiger H.C., Phillips A.G. Effects of neurotension on dopamine release and metabolism in the rat striatum and nucleus accumbens: cross validation using in vivo voltammetry and microdialysis. Neuroscience. 1990;34:699–705. doi: 10.1016/0306-4522(90)90176-5. [DOI] [PubMed] [Google Scholar]
- 3.Bradberry C.W., Roth R.H. Cocaine increases extracellular dopamine in rat nucleus accumbens and ventral tegmental area as shown by in vivo microdialysis. Neurosci. Lett. 1989;103:97–102. doi: 10.1016/0304-3940(89)90492-8. [DOI] [PubMed] [Google Scholar]
- 4.Broderick P.A. Striatal neurochemistry of dynorphin-(1–13): In vivo electrochemical semidifferential analyses. Neuropeptides. 1987;10:369–386. doi: 10.1016/s0143-4179(87)90128-4. [DOI] [PubMed] [Google Scholar]
- 5.Broderick P.A. Characterizing stearate probes in vitro for the electrochemical detection of dopamine and serotonin. Brain Res. 1989;495:115–121. doi: 10.1016/0006-8993(89)91224-9. [DOI] [PubMed] [Google Scholar]
- 6.Broderick P.A. State-of-the-Art microelectrodes for in vivo voltammetry. Electroanalysis. 1990;2:241–251. [Google Scholar]
- 7.Broderick P.A. Cocaine: on-line analysis of an accumbens amine neural basis for psychomotor behavior. Pharmacol. Biochem. Behav. 1991;40:959–968. doi: 10.1016/0091-3057(91)90112-F. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8.Carboni E., Imperato A., Perezzani L., DiChiara G. Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats. Neuroscience. 1989;28:653–661. doi: 10.1016/0306-4522(89)90012-2. [DOI] [PubMed] [Google Scholar]
- 9.Carlsson A., Kehr W., Lindqvist M., Magnusson T., Atack C.V. Regulation of monoamine metabolism in the central nervous system. Pharmacol. Rev. 1972;24:371–384. [PubMed] [Google Scholar]
- 10.Church W.H., Justice J.B., Jr., Byrd L.D. Extracellular dopamine in rat striatum following uptake inhibition by cocaine, nomifensine and benztropine. Eur. J. Pharmacol. 1987;139:345–348. doi: 10.1016/0014-2999(87)90592-9. [DOI] [PubMed] [Google Scholar]
- 11.Cunningham K.A., Lakoski J.M. Electrophysiological effects of cocaine and procaine on dorsal raphe serotonin neurons. Eur. J. Pharmacol. 1988;148:457–462. doi: 10.1016/0014-2999(88)90128-8. [DOI] [PubMed] [Google Scholar]
- 12.deWit H., Wise R.A. Blockade of cocaine reinforcement in rats with the dopamine receptor blocker pimozide but not with the noradrenergic blockers, phentolamine or phenoxybenzamine. Can. J. Psychol. 1977;31:195–203. doi: 10.1037/h0081662. [DOI] [PubMed] [Google Scholar]
- 13.Fischman M.W. The behavioral pharmacology of cocaine in humans. Cocaine: Pharmacology, effects and treatment of abuse. NIDA Res. Monogr. Ser. 1984;50:72–91. [PubMed] [Google Scholar]
- 14.Gessa G.L., Vargiu L., Crabai F., Boero G.C., Caboni F., Camba R. Selective increase of brain dopamine induced by gamma-hydroxybutyrate. Life Sci. 1966;5:1921–1930. [Google Scholar]
- 15.Heikkila R.E., Orlansky H., Cohen G. Studies on the distinction between uptake inhibition and release of [3H] dopamine in rat brain tissue slices. Biochem. Pharmacol. 1975;24:847–852. doi: 10.1016/0006-2952(75)90152-5. [DOI] [PubMed] [Google Scholar]
- 16.Hernandez L., Hoebel B.G. Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci. 1988;42:1705–1712. doi: 10.1016/0024-3205(88)90036-7. [DOI] [PubMed] [Google Scholar]
- 17.Izenwasser S., Cox B.M. Repeated cocaine administration has differential effects on serotonin and dopamine uptake in rat striatum and nucleus accumbens. NIDA Res. Monogr. 1991 in press. [Google Scholar]
- 18.Kalivas P.W., Duffy P. Effect of acute and daily cocaine treatment on extracellular dopamine in the nucleus accumbens. Synapse. 1990;5:48–58. doi: 10.1002/syn.890050104. [DOI] [PubMed] [Google Scholar]
- 19.Kleven M.S., Anthony E.W., Goldberg L.I., Woolverton W.L. Blockade of the discriminative stimulus effects of cocaine in rhesus monkeys with the D1 dopamine antagonist SCH23390. Psychopharmacology (Berlin) 1988;95:427–429. doi: 10.1007/BF00181961. [DOI] [PubMed] [Google Scholar]
- 20.Leceese A.P., Lyness W.H. The effects of putative 5-hydroxytryptamine receptor active agents on D-amphetamine self-administration in controls and rats with 5,7-dihydroxytryptamine median forebrain bundle lesions. Brain Res. 1984;303:153–162. doi: 10.1016/0006-8993(84)90223-3. [DOI] [PubMed] [Google Scholar]
- 21.Nomikos G.G., Damsma G., Wenkstern D., Fibiger H.C. In vivo characterization of locally applied dopamine uptake inhibitors by striatal microdialysis. Synapse. 1990;6:106–112. doi: 10.1002/syn.890060113. [DOI] [PubMed] [Google Scholar]
- 22.Pani L., Kuzmin A., Diana M., De-Montis G., Gessa G.L., Rossetti Z.L. Calcium receptor antagonists modify cocaine effects in the central nervous system differently. Eur. J. Pharmacol. 1990;190(1–2):217–221. doi: 10.1016/0014-2999(90)94128-k. [DOI] [PubMed] [Google Scholar]
- 23.Pelligrino L.J., Cushman A.J. Appleton-Century-Crofts; New York: 1967. A stereotaxic atlas of the rat brain; p. 19. [Google Scholar]
- 24.Pettit H.O., Justice J.B., Jr. Effects of dose on cocaine self-administration behavior and dopamine levels in the nucleus accumbens. Brain Res. 1991;539:94–102. doi: 10.1016/0006-8993(91)90690-w. [DOI] [PubMed] [Google Scholar]
- 25.Porrino L.J., Ritz M.C., Goodman N.L., Sharpe L.G., Kuhar M.J., Goldberg S.R. Differential effects of the pharmacological manipulation of serotonin systems on cocaine and amphetamine self-administration in rats. Life Sci. 1989;45:1529–1535. doi: 10.1016/0024-3205(89)90418-9. [DOI] [PubMed] [Google Scholar]
- 26.Risner M.E., Jones B.E. Intravenous self-administration of cocaine and norcocaine by dogs. Psychopharmacology (Berlin) 1980;71:83–89. doi: 10.1007/BF00433258. [DOI] [PubMed] [Google Scholar]
- 27.Ritz M.C., Kuhar M.J. Relationship between self-administration of amphetamines and monoamine receptors in brain: comparison with cocaine. J. Pharmacol. Exp. Ther. 1989;248:1010–1017. [PubMed] [Google Scholar]
- 28.Roberts D.C.S., Koob G.F., Klonoff P., Fibiger H.C. Extinction and recovery of cocaine self-administration following 6-hydroxydopamine lesions of the nucleus accumbens. Pharmacol. Biochem. Behav. 1980;12:781–787. doi: 10.1016/0091-3057(80)90166-5. [DOI] [PubMed] [Google Scholar]
- 29.Roth R.H., Suhr Y. Mechanism of the γ-hydroxybutyrate induced increase in brain dopamine and its relationship to “sleep”. Biochem. Pharmacol. 1970;19:3001–3012. doi: 10.1016/0006-2952(70)90086-9. [DOI] [PubMed] [Google Scholar]
- 30.Rothman R.B., Mele A., Reid A.A., Akunne H., Greig N., Thurkauf A., Rice K.C., Pert A. Tight binding dopamine reuptake inhibitors as cocaine antagonists. A strategy for drug development. FEBS Lett. 1989;257:341–344. doi: 10.1016/0014-5793(89)81566-2. [DOI] [PubMed] [Google Scholar]
- 31.Scheel-Kruger J., Baestrup C., Nielson M., Golembiowska K., Mogilnicka E. Cocaine: discussion on the role of dopamine in the biochemical mechanism of action. In: Ellinwood E.H., Kilbey M.M., editors. second edition. vol. 21. Plenum Press; New York: 1977. pp. 373–407. (Cocaine and other stimulants. Advances in behavioral biology). [Google Scholar]
- 32.Seiden L.S., Kleven M.S. Lack of toxic effects of cocaine on dopamine and serotonin neurons in the rat brain. NIDA Res. Monogr. 1988;88:276–289. [PubMed] [Google Scholar]
- 33.Spealman R.D., Kelleher R.T. Self-administration of cocaine and two cocaine analogs on scheduled-controlled behavior of squirrel monkeys. J. Pharmacol. Exp. Ther. 1977;202:500–509. [PubMed] [Google Scholar]
- 34.Stamford J.A., Kruk Z.L., Millar J. Stimulated limbic and striatal dopamine release measured by fast cyclic voltammetry: anatomical, electrochemical and pharmacological characterization. Brain Res. 1988;454:282–288. doi: 10.1016/0006-8993(88)90828-1. [DOI] [PubMed] [Google Scholar]
- 35.Walters J.R., Roth R.H. Effect of gamma-hydroxybutyrate on dopamine and dopamine metabolites in the rat striatum. Biochem. Pharmacol. 1972;21:2111–2121. doi: 10.1016/0006-2952(72)90164-5. [DOI] [PubMed] [Google Scholar]
- 36.Walters J.R., Roth R.H. Dopaminergic neurons: drug-induced antagonism of the increase in tyrosine hydroxylase activity produced by cessation of impulse flow. J. Pharmacol. Exp. Ther. 1974;191:82–91. [PubMed] [Google Scholar]
- 37.Wilson M.C., Schuster C.R. The effects of chlorpromazine on psychomotor stimulant self administration in the rhesus monkey. Psychopharmacology (Berlin) 1972;26:115–126. doi: 10.1007/BF00422098. [DOI] [PubMed] [Google Scholar]
- 38.Winters W.D., Spooner C.E. Various seizure activities following gamma-hydroxybutyrate. Int. J. Neuropharmacol. 1965;4:197–200. doi: 10.1016/0028-3908(65)90034-1. [DOI] [PubMed] [Google Scholar]