Skip to main content
Log in

Biochemical Parameters of Dopaminergic and GABAergic Neurotransmission in the CNS of Roman High-Avoidance and Roman Low-Avoidance Rats

  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

The dopaminergic (DAergic) and GABAergic pathways in the central nervous system (CNS) are involved in the control of emotions, in the reactivity to stressful stimuli, and in the positive and negative reinforcing properties of psychotropic drugs. In the present review, we summarize the differences in a range of neurochemical markers of GABA- and DA-mediated neurotransmission in the CNS of Roman high-avoidance (RHA/Verh) and Roman low-avoidance (RLA/Verh) rats, two psychogenetically selected lines that differ in what may be considered to be level of emotionality. The stimulatory effect of GABA on 36Cl uptake was less pronounced in the cerebral cortex of RLA/Verh rats compared to RHA/Verh rats. In addition, the binding affinity of [35S]TBPS, a selective ligand of the convulsant site located in the chloride channel of GABAA receptors, was significantly lower in the hippocampus of RLA/Verh rats than in their high-avoidance counterparts. On the other hand, the density of D1 DA receptors labeled with [3H]SCH 23390 was lower in the nucleus accumbens of RLA/Verh rats compared to RHA/Verh rats. Brain microdialysis studies demonstrated that tail-pinch stress and subconvulsant doses of the anxiogenic compound pentylenetetrazol increased the extracellular concentrations of DA in the prefrontal cortex of hypoemotive RHA/Verh rats but not in their hyperemotive RLA/Verh counterparts. These line-dependent differences in GABAergic and DAergic neurotransmission may contribute to the distinct emotionality and responsiveness to centrally active drugs of RHA/Verh and RLA/Verh rats.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  • Abercrombie, E. D., Keefe, K. A., DiFrischia, D. S., and Zigmond, M. J. (1989). Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens, and medial frontal cortex. J. Neurochem. 52:1655–1658.

    Google Scholar 

  • Acquas, E., Carboni, E., Leone, P., and Di Chiara, G. (1989). SCH 23390 blocks drug-conditioned place-preference and place-aversion: Anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade? Psychopharmacology 99:151–155.

    Google Scholar 

  • Bassareo, V., Tanda, G., Petromilli, P., Giua, C., and Di Chiara, G. (1996). Nonpsychostimulant drugs of abuse and anxiogenic drugs activate with differential selectivity dopamine transmission in the nucleus accumbens and in the medial prefrontal cortex of the rat. Psychopharmacology 124:293–299.

    Google Scholar 

  • Biggio, G., Concas, A., Corda, M. G., Giorgi, O., Sanna, E., and Serra, M. (1990). GABAergic and dopaminergic transmission in the rat cerebral cortex: Effect of stress, anxiolytic and anxiogenic drugs. Pharmac. Ther. 48:121–142.

    Google Scholar 

  • Bignami, G. (1965). Selection for high rates and low rates of avoidance conditioning in the rat. Anim. Behav. 13:221–227.

    Google Scholar 

  • Bradberry, C. W., Lory, J. D., and Roth, R. H. (1991). The anxiogenic β-carboline FG 7142 selectively increases dopamine release in rat prefrontal cortex as measured by microdialysis. J. Neurochem. 56:748–752.

    Google Scholar 

  • Burt, D. R. (1994). GABAA receptor-activated chloride channels. In Guggino, W. B. (ed.), Current Topics in Membranes, Academic Press, San Diego, pp. 215–263.

    Google Scholar 

  • Cherubini, E., Gaiarsa, J.-L., and Ben-Ari, Y. (1991). GABA: An excitatory transmitter in early postnatal life. Trends Neurosci. 14:515–519.

    Google Scholar 

  • Cools, A. R., Brachten, R., Heeren, D., Willemen, A., and Ellenbroek, B. (1990). Search after neurobiological profile of individual specific features of Wistar rats. Brain Res. Bull. 24:49–69.

    Google Scholar 

  • Corda, M. G., Blaker, W. D., Mendelson, W. B., Guidotti, A., and Costa, E. (1983). β-Carbolines enhance shock-induced suppression of drinking in rats. Proc. Natl. Acad. Sci. USA 80:2072–2076.

    Google Scholar 

  • Corda, M. G., Giorgi, O., Longoni, B., Orlandi, M., and Biggio, G. (1990). Decrease in the function of the γ-aminobutyric acid-coupled chloride channel produced by the repeated administration of pentylenetetrazol to rats. J. Neurochem. 55:1216–1221.

    Google Scholar 

  • Corda, M. G., Orlandi, M., Lecca, D., and Giorgi, O. (1992). Decrease in GABAergic function induced by pentylenetetrazol kindling in rats: Antagonism by MK-801. J. Pharmacol. Exp. Ther. 262:792–800.

    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 

  • Crabbe, J. C., and Belknap, J. K. (1992). Genetic approaches to drug dependence. Trends Pharmacol. Sci. 13:212–219.

    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. 451:237–247.

    Google Scholar 

  • Deutch, A. Y., Tam, S. Y., and Roth, R. H. (1985). Foot shock and conditioned stress increase 3,4-dihydroxyphenylacetic acid (DOPAC) in the ventral tegmental area but not substantia nigra. Brain Res. 333:143–146.

    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., Tanda, G., Frau, R., and Carboni, E. (1993). On the preferential release of dopamine in the nucleus accumbens by amphetamine: Further evidence obtained by vertically implanted concentric dialysis probes. Psychopharmacology 112:398–402.

    Google Scholar 

  • Drago, J., Gerfen, C. R., Lachowicz, J. E., Steiner, H., Hollon, T. R., Love, P. E., Ooi, G. T., Grinberg, A., Lee, E. J., Huang, S. P., Bartlett, P. F., Jose, P. A., Sibley, D. R., and Westphal, H. (1994). Altered striatal function in a mutant mouse lacking D1A dopamine receptors. Proc. Natl. Acad. Sci. USA 91:12564–12568.

    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., Ferré, P., Fernández-Teruel, A., Levi de Stein, M., Wolfman, C., Medina, J. H., Tobeña, A., and Escorihuela, R. M. (1995). Effects of prenatal diazepam on two-way avoidance behavior, swimming navigation and brain levels of benzodiazepine-like molecules in male Roman high-and low-avoidance rats. Psychopharmacology 122:51–57.

    Google Scholar 

  • Drugan, R. G., Morrow, A. L., Weizman, R., Weizman, A., Deutsch, S. I., Crawley, J. N., and Paul, S. M. (1989). Stress-induced behavioral depression in the rat is associated with a decrease in GABA receptor-mediated chloride ion flux and brain benzodiazepine receptor occupancy. Brain Res. 487:45–51.

    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 

  • Fernández-Teruel, A., Escorihuela, R. M., Tobeña, A., and Driscoll, P. (1991). Stress and putative endogenous ligands for benzodiazepine receptors: The importance of characteristics of the aversive situation and of differential emotionality in experimental animals. Experientia 47:1051–1056.

    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 Feer, H. (1981). [3H]Diazepam binding sites in roman high-and low-avoidance rats. Experientia 37:1315–1316.

    Google Scholar 

  • Giorgi, O., Corda, M. G., and Biggio, G. (1988). Ro 15-4513, like anxiogenic β-carbolines, increases dopamine metabolism in the prefrontal cortex of the rat. Eur. J. Pharmacol. 156:71–75.

    Google Scholar 

  • Giorgi, O., Pibiri, M. G., Dal Toso, R., and Ragatzu, G. (1992). Age-related changes in the turnover rates of D1-dopamine receptors in the retina and in distinct areas of the rat brain. Brain Res. 569:323–329.

    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 

  • Giorgi, O., Lecca, D., Cancedda, E., Serra, G. P., and Corda, M. G. (1995a). Modulation of [35S]TBPS binding by ligands with preferential affinity for benzodiazepine BZ1 sites in the cerebral cortex of newborn and adult rats. Eur. J. Pharmacol. 290:37–47.

    Google Scholar 

  • Giorgi, O., Lecca, D., Carboni, G., Frau, V., Valentini, V., Fernández, A., Di Chiara, G., and Corda, M. G. (1995b). Stress and pentylenetetrazol increase the release of dopamine in the prefrontal cortex of Roman high-avoidance (RHA) but not low-avoidance (RLA) rats. Neurosci. Meet. Abstr. 21:1685.

    Google Scholar 

  • Giorgi, O., Orlandi, M., Lecca, D., Serra, G. P., Zhang, L., and Corda, M. G. (1996). Kinetics of [35S]t-Butylbicyclophosphorothionate binding in the cerebral cortex of newborn and adult rats: effects of GABA and receptor desensitization. J. Neurochem. 67:423–429.

    Google Scholar 

  • Giorgi, O., Corda, M. G., Carboni, G., Frau, V., and Di Chiara, G. (1997). Effects of cocaine and morphine in rats from two psychogenetically selected lines: A behavioral and brain dialysis study. Behav. Genet. 27:537–546.

    Google Scholar 

  • Iorio, L. C., Barnett, A., Leitz, F. H., Houser, V. P., and Korduba, C. A. (1983). SCH 23390, a potential benzazepine antipsychotic with unique interactions on dopaminergic systems. J. Pharmacol. Exp. Ther. 226:462–468.

    Google Scholar 

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

    Google Scholar 

  • Lal, H., and Emmett-Oglesby, M. W. (1983). Behavioral analogues of anxiety. Animal models. Neuropharmacology 22:1423–1441.

    Google Scholar 

  • Lambert, J. J., Belelli, D., Hill-Venning, C., and Petyers, J. A. (1995). Neurosteroids and GABAA receptor function. Trends Pharmacol. Sci. 16:295–303.

    Google Scholar 

  • Laurie, D. J., Wisden, W., and Seeburg, P. H. (1992). The distribution of thirteen GABAA receptor subunit mRNAs in the rat brain. III. Embryonic and postnatal development. J. Neurosci. 12:4151–4172.

    Google Scholar 

  • Le Moal, M., Galey, D., and Cardo, B. (1975). Behavioral effects of local injection of 6-hydroxydopamine in the medial ventral tegmentum in the rat. Possible role of the mesolimbic dopaminergic system. Brain Res. 88:190–194.

    Google Scholar 

  • Lindvall, O., and Bjorklund, A. (1983). Dopamine-and norepinephrine-containing neuron systems: Their anatomy in the brain. In Emson, P. C. (ed.), Chemical Neuroanatomy, Raven Press, New York, pp. 229–255.

    Google Scholar 

  • Lowry, O. H., Rosebrough, N. J., Farr, A. L., and Randall, R. J. (1951). Protein measurement with the Folin phenol reagent. J. Biol. Chem. 193:265–275.

    Google Scholar 

  • Macdonald, R. L., and Barker, J. L. (1977). Pentylenetetrazol and penicillin are selective antagonists of GABA-mediated postsynaptic inhibition of cultured mammalian neurons. Nature 267:720–721.

    Google Scholar 

  • Macdonald, R. L., and Olsen, R. W. (1994). GABAA receptor channels. Annu. Rev. Neurosci. 17:569–602.

    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 

  • Martin, J. R., Oettinger, R., Driscoll, P., Buzzi, R., and Battig, K. (1982). Effects of chlordiazepoxide and imipramine on maze patrolling within two different maze configurations by psychogenetically selected lines of rats. Psychopharmacology 78:58–62.

    Google Scholar 

  • McIntyre, T., and Skolnick, P. (1991). t-[3535] Butylbicyclophosphorothionate binding under equilibrium and nonequilibrium conditions: Differential effects of barbiturates and γ-aminobutyric acid in the long-sleep and short-sleep selected mouse lines. J. Neurochem. 56:287–293.

    Google Scholar 

  • Mogenson, G. J. (1987). Limbic-motor integration. Prog. Psychobiol. Physiol. Psych. 12:117–170.

    Google Scholar 

  • Munson, P. J., and Rodbard, D. (1980). Ligand: A versatile computerized approach to characterization of ligand-binding systems. Anal. Biochem. 107:220–239.

    Google Scholar 

  • Overstreet, D. H., Rezvani, A. H., and Janowsky, D. S. (1992). Genetic animal models of depression and ethanol preference provide support for cholinergic and serotonergic involvement in depression and alcoholism. Biol. Psychiatry 31:919–936.

    Google Scholar 

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

    Google Scholar 

  • Pellow, S., and File, S. E. (1986). Anxiolytic and anxiogenic drug effects on exploratory activity in an elevated plus-maze: A novel test of anxiety in the rat. Pharmacol. Biochem. Behav. 24:525–529.

    Google Scholar 

  • Prado de Carvalho, L., Greksch, G., Chapoutier, G., and Rossier, J. (1983). Anxiogenic and non-anxiogenic benzodiazepine antagonists. Nature 301:64–66.

    Google Scholar 

  • Razafimanalina, R., Mormède, P., and Velley, L. (1996). Gustatory preference-aversion profiles for saccharin, quinine and alcohol in Roman high-and low-avoidance lines. Behav. Pharmacol. 7:78–84.

    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 

  • Shephard, R. A., Nielsen, E. B., and Broadhurst, P. L. (1982). Sex and strain differences in benzodiazepine receptor binding in Roman rat strains. Eur. J. Pharmacol. 77:327–330.

    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 

  • Sieghart, W. (1995). Structure and pharmacology of γ-aminobutyric acidA receptor subtypes. Pharmacol. Rev. 47:181–234.

    Google Scholar 

  • Simon, H., and Le Moal, M. (1988). Mesencephalic dopaminergic neurons: Role in the general economy of the brain. Ann. N.Y. Acad. Sci. 537:235–253.

    Google Scholar 

  • Simon, H., Scatton, B., and Le Moal, M. (1980). Dopaminergic A10 neurones are involved in cognitive functions. Nature 286:150–151.

    Google Scholar 

  • Squires, R. F., Casida, J. E., Richardson, M., and Saederup, E. (1983). [35S]t-Butylbicyclophosphorothionate binds with high affinity to brain specific sites coupled to γ-aminobutyric acid-A and ion recognition sites. Mol. Pharmacol. 23:326–336.

    Google Scholar 

  • Steimer, T., Driscoll, P., and Schulz, P. E. (1997). Brain metabolism of progesterone, coping behaviour and emotional reactivity in male rats from two psychogenetically selected lines. J. Neuroendocrinol. 9:169–175.

    Google Scholar 

  • Vogel, W. H. (1985). Coping, stress, stressors and health consequences. Neuropsychobiology 13:129–135.

    Google Scholar 

  • Willig, F., M'Harzi, M., Bardelay, C., Viet, D., and Delacour, J. (1991). Roman strains as a psychogenetic model for the study of working memory: Behavioral and biochemical data. Pharmacol. Biochem. Behav. 40:7–16.

    Google Scholar 

  • Xu, M., Hu, X.-T., Coper, D. C., Moratalla, R., Graybiel, A. M., White, F. J., and Tonegawa, S. (1994). Elimination of cocaine-induced hyperactivity and dopamine-mediated neurophysiological effects in dopamine Dl receptor mutantmice. Cell 79:945–955.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Corda, M.G., Lecca, D., Piras, G. et al. Biochemical Parameters of Dopaminergic and GABAergic Neurotransmission in the CNS of Roman High-Avoidance and Roman Low-Avoidance Rats. Behav Genet 27, 527–536 (1997). https://doi.org/10.1023/A:1021452814574

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1021452814574

Navigation