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Effects of Cocaine and Morphine in Rats from Two Psychogenetically Selected Lines: A Behavioral and Brain Dialysis Study

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Abstract

The Swiss sublines of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats differ in their reactivity to environmental and pharmacological stressors, in their sensitivity to stereotypies elicited by dopamine (DA)-mimetic agents, and in their densities of D1 DA receptors in the terminal field of the mesoaccumbens DAergic projection, an important link in the neural networks involved in the motor effects and reinforcing properties of drugs abused by humans. The present study was therefore designed to compare the behavioral and neurochemical effects of cocaine (5 mg/kg, i.p.) and morphine (0.5 mg/kg, s.c.) in RHA/Verh and RLA/Verh rats. To this aim, we measured motor activity and DA output in the nucleus accumbens as determined by brain microdialysis. The number of counts corresponding to horizontal, vertical, and total motor activities accumulated in basal conditions during the 60-min acclimation period was significantly larger in RHA/Verh than in RLA/Verh rats. Moreover, horizontal, vertical, and total motor activities throughout the 120-min observation period that followed the administration of vehicle tended to be larger in RHA/Verh rats, although the difference between the two lines was not statistically significant. In RHA/Verh rats, locomotion, rearing, and total motor activity were significantly more intense after acute cocaine and morphine challenges than after vehicle administration, whereas no significant differences in motor activity were observed between control and cocaine- or morphine-treated RLA/Verh rats. No line-related differences were detected in the basal DA output, but the effect of cocaine on DA release was more robust in RHA/Verh rats. Likewise, the effect of morphine was more pronounced in RHA/Verh than in RLA/Verh rats. Because the mesoaccumbens DAergic pathway plays a central role in the acquisition of motivational valence by environmental and pharmacological stimuli and, therefore, in operant behavior, our results suggest that comparative behavioral and neurochemical studies in these two lines may provide useful information on the biological correlates of drug dependence.

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REFERENCES

  • Acquas, E., and Di Chiara, G. (1994). D1 receptor blockade stereospecifically impairs the acquisition of drug-conditioned place preference and place aversion. Behav. Pharmacol. 5:555–569.

    Google Scholar 

  • Alheid, G. F., and Heimer, L. (1988). New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: The striopallidal, amygdaloid, and corticopetal components of the substantia innominata. Neuroscience 27:1–39.

    Google Scholar 

  • Asher, I. M., and Aghajanian, G. K. (1974). 6-Hydroxydopamine lesions of olfactory tubercles and caudate nuclei: Effect on amphetamine-induced stereotyped behavior in rats. Brain Res 82:1–12.

    Google Scholar 

  • Corda, M. G., Giorgi, O., Lecca, D., Carboni, G., Frau, V., Piras, G., Valentini, V., and Di Chiara, G. (1995). Amphetamine, cocaine, and morphine produce larger increases in dopamine release in the nucleus accumbens of Roman high-avoidance versus low-avoidance rats. Neurosci. Meet. Abstr. 21:971.

    Google Scholar 

  • Corda, M. G., Lecca, D., Piras, G., Di Chiara, G., and Giorgi, O. (1997). Biochemical parameters of dopaminergic and GABAergic neurotransmission in the CNS of Roman high-avoidance and Roman low-avoidance rats. Behav. Genet. 27:527–536.

    Google Scholar 

  • D'Angio, M., Serrano, A., Driscoll, P., and Scatton, B. (1988). Stressful environmental stimuli increase extracellular DOPAC levels in the prefrontal cortex of hypoemotional (Roman high-avoidance) but not hyperemotional (Roman low-avoidance) rats. An in vivo voltammetric study. Brain Res. 45:237–247.

    Google Scholar 

  • Delfs, J. M., Schreiber, L., and Kelley, A. E. (1990). Microinjection of cocaine into the nucleus accumbens elicits locomotor activation in the rat. J. Neurosci. 10:303–310.

    Google Scholar 

  • Deutch, A. Y., Bourdelais, A. J., and Zahm, D. S. (1993). The nucleus accumbens core and shell: Accumbal compartments and their functional attributes. In Kalivas, P. W., and Barnes, C. D. (eds.), Limbic Motor Systems and Neuropsychiatry, CRC Press, Boca Raton, FL, pp. 45–88.

    Google Scholar 

  • Di Chiara, G. (1995). The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend. 38:95–137.

    Google Scholar 

  • Di Chiara, G., and Imperato, A. (1988). Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc. Natl. Acad. Sci. USA 85:5274–5278.

    Google Scholar 

  • Di Chiara, G., and North, R. A. (1992). Neurobiology of opiate abuse. Trends Pharmacol. Sci. 13:185–193.

    Google Scholar 

  • Driscoll, P. (1986). Roman high-and low-avoidance rats: present status of the Swiss sublines, RHA/Verh and RLA/Verh, and effects of amphetamine on shuttle-box performance. Behav. Genet. 16:355–364.

    Google Scholar 

  • Driscoll, P., and Battig, K. (1982). Behavioral, emotional and neurochemical profiles of rats selected for extreme differences in active, two-way avoidance performance. In Lieblich, I. (ed.), Genetics of the Brain, Elsevier, Amsterdam, pp. 95–123.

    Google Scholar 

  • Driscoll, P., and Stubi, R. (1985). Dose-related effects of pentobarbital on the genetic differences seen between paired, Roman high-or low-avoidance rats in a shuttle box. Pharmacol. Biochem. Behav. 22:435–439.

    Google Scholar 

  • Driscoll, P., Dedek, J., Fuchs, A., and Gentsch, C. (1985). Stereotypic, hypothermic, and central dopaminergic effects of apomorphine in Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats. Behav. Genet. 15:591–592.

    Google Scholar 

  • Driscoll, P., Lieblich, I., and Cohen, E. (1986). Amphetamine-induced stereotypic responses in Roman high-and low-avoidance rats. Pharmacol. Biochem. Behav. 24:1329–1332.

    Google Scholar 

  • Driscoll, P., Dedek, J., D'Angio, M., Claustre, Y., and Scatton, B. (1990). A genetically-based model for divergent stress responses: Behavioral, neurochemical and hormonal aspects. In Pliska, I., and Stranzinger, G. (eds.), Farm Animals in Biomedical Research, Verlag Paul Parey, Hamburg, pp. 97–107.

    Google Scholar 

  • Durcan, M. J., Fulker, D. W., and Campbell, I. C. (1984). Differences in the stereotypy response but not the hypomotility response to apomorphine in the Roman high and low avoiding strains of rats. Psychopharmacology 82:215–220.

    Google Scholar 

  • Escorihuela, R. M., Tobeña, A., Driscoll, P., and Fernández-Teruel, A. (1995). Effects of training, early handling, and perinatal flumazenil on shuttle box acquisition in Roman low-avoidance rats: toward overcoming a genetic deficit. Neurosci. Biobehav. Rev. 19:353–367.

    Google Scholar 

  • Fallon, J. H. (1988). Topographic organization of ascending dopaminergic projections. Ann. N.Y. Acad. Sci. 537:1–9.

    Google Scholar 

  • Ferré, P., Fernández-Teruel, A., Escorihuela, R. M., Driscoll, P., Corda, M. G., Giorgi, O., and Tobeña, A. (1995). Behavior of the Roman/Verh high-and low-avoidance rat lines in anxiety tests: Relationship with defecation and self-grooming. Physiol. Behav. 58:1209–1213.

    Google Scholar 

  • Gentsch, C., Lichtsteiner, M., and Driscoll, P. (1989a). Apomorphine-induced gnawing and licking: a comparison between RHA/Verh and RLA/Verh rats. Eur. J. Neurosci. Suppl. 2:315.

    Google Scholar 

  • Gentsch, C., Lichtsteiner, M., Siegfried, B., Frischknecht, H. R., and Driscoll, P. (1989b). Novelty-induced analgesia (NIA) in Roman high-and low-avoidance (RHA/Verh and RLA/Verh) rats. Behav. Genet. 19:757.

    Google Scholar 

  • Gessa, G. L., Muntoni, F., Collu, M., Vargiu, L., and Mereu, G. (1985). Low doses of ethanol activate dopaminergic neurons in the ventral tegmental area. Brain Res. 348:201–203.

    Google Scholar 

  • Giorgi, O., Orlandi, M., Escorihuela, R. M., Driscoll, P., Lecca, D., and Corda, M. G. (1994). GABAergic and dopaminergic transmission in the brain of Roman high-avoidance and Roman low-avoidance rats. Brain Res. 638:133–138.

    Google Scholar 

  • Harris, R. A., Brodie, M. S., and Dunwiddie, T. V. (1992). Possible substrates of ethanol reinforcement: GABA and dopamine. Ann. N.Y. Acad. Sci. 537:235–253.

    Google Scholar 

  • Heimer, L., de Olmos, J., Alheid, G. F., and Zaborsky, L. (1991). “Perestroika” in the basal forebrain: opening the border between neurology and psychiatry. Prog. Brain Res. 87:109–169.

    Google Scholar 

  • Iversen, S. D. (1977). Brain dopamine systems and behaviour. In Iversen, L. L., Iversen, S. D., and Snyder, S. H. (eds.), Handbook of Psychopharmacology, Vol. 8, Plenum Press, New York, pp. 333–384.

    Google Scholar 

  • Izenwasser, S., Werling, L. L., and Cox, B. M. (1990). Comparison of the effects of cocaine and other inhibitors of dopamine uptake in rat striatum, nucleus accumbens, olfactory tubercle, and medial prefrontal cortex. Brain Res. 520:303–309.

    Google Scholar 

  • Johnson, S. W., and North, R. A. (1992). Opioids excite dopamine neurons by hyperpolarization of local interneurons. J. Neurosci. 12:483–488.

    Google Scholar 

  • Kelley, P. H., and Iversen, S. D. (1975). Selective 6-OHDA-induced destruction of mesolimbic dopamine neurons: Abolition of psychostimulant-induced locomotor activity in rats. Eur. J. Pharmacol. 40:45–56.

    Google Scholar 

  • Koob, G. F. (1992). Drugs of abuse: Anatomy, pharmacology and function of reward pathways. Trends Pharmacol. Sci. 13:177–184.

    Google Scholar 

  • Koob, G. F., Simon, H., Herman, J. P., and LeMoal, M. (1984). Neuroleptic-like disruption of the conditioned avoidance response requires destruction of both the mesolimbic and nigro-striatal dopamine systems. Brain Res. 303:319–329.

    Google Scholar 

  • Markou, A., Weiss, F., Gold, L. H., Caine, S. B., Schulteis, G., and Koob, G. F. (1993). Animal models of drug craving. Psychopharmacology 112:163–182.

    Google Scholar 

  • Matthews, R. T., and German, D. C. (1984). Electrophysiological evidence for excitation of rat ventral tegmental area dopamine neurons by morphine. Neuroscience 11:617–625.

    Google Scholar 

  • Mereu, G., Yoon, K. W., Boi, V., Gessa, G. L., Naes, L., and Westfall, T. C. (1987). Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine. Eur. J. Pharmacol. 141:395–399.

    Google Scholar 

  • Paxinos, G., and Watson, C. (1987). The Rat Brain in Stereotaxic Coordinates, Academic Press, London.

    Google Scholar 

  • Pontieri, F. E., Tanda, G., and Di Chiara, G. (1995). Intravenous cocaine, morphine, and amphetamine preferentially increase extracellular dopamine in the “shell” as compared with the “core” of the rat nucleus accumbens. Proc. Natl. Acad. Sci. USA 92:12304–12308.

    Google Scholar 

  • Pontieri, F. E., Tanda, G., Orzi, F., and Di Chiara, G. (1996). Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 382:255–257.

    Google Scholar 

  • Robbins, T. W., and Everitt, B. J. (1992). Functions of dopamine in the dorsal and ventral striatum. Semin. Neurosci. 4:119–127.

    Google Scholar 

  • Samson, H. H., and Harris, R. A. (1992). Neurobiology of alcohol abuse. Trends Pharmacol. Sci. 13:212–219.

    Google Scholar 

  • Scheel-Kruger, J., Graestrup, C., Nielson, M., Golembiowski, K., and Mogilmicka, E. (1977). Cocaine: Discussion on the role of dopamine in the biochemical mechanism of action. In Ellinwood, E., Jr., and Kilby, M. (eds.), Cocaine and Other Stimulants, Plenum Press, New York, pp. 373–407.

    Google Scholar 

  • Shippenberg, T. S., Bals-Kubik, R., Huber, A., and Herz, A. (1991). Neuroanatomical substrates mediating the aversive effects of D-1 dopamine receptor antagonists. Psychopharmacology 103:209–214.

    Google Scholar 

  • Siegfried, B., Frischknecht, H. R., Lazega, D., and Driscoll, P. (1989). Morphine effects on body temperature and behavior in Roman high-and low-avoidance (RHA/Verh and RLA/Verh) rats. Behav. Genet. 19:775.

    Google Scholar 

  • Stolerman, I. (1992). Drugs of abuse: Behavioural principles, methods and terms. Trends Pharmacol. Sci. 13:170–176.

    Google Scholar 

  • Woolverton, W. L., and Johnson, K. M. (1992). Neurobiology of cocaine abuse. Trends Pharmacol. Sci. 13:193–200.

    Google Scholar 

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Giorgi, O., Corda, M.G., Carboni, G. et al. Effects of Cocaine and Morphine in Rats from Two Psychogenetically Selected Lines: A Behavioral and Brain Dialysis Study. Behav Genet 27, 537–546 (1997). https://doi.org/10.1023/A:1021405031412

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