, Volume 109, Issue 3, pp 379–382

Anxiogenic drugs beta-CCE and FG 7142 increase extracellular dopamine levels in nucleus accumbens

  • L. D. McCullough
  • J. D. Salamone
Rapid Communications


Two experiments were conducted to study the effects of anxiogenic drugs on dopamine release and metabolism in nucleus accumbens. Microdialysis probes were implanted into the nucleus accumbens, and rats were tested the day after implantation. In the first experiment, groups of rats received injections of saline, 1.25 or 2.5 mg/kg beta-CCE. In the second experiment, groups of rats received injections of saline, 10.0, 20.0 or 30.0 mg/kg FG-7142. Both drugs produced significant increases in dopamine release and metabolism in nucleus accumbens. Neither drug had significant effects on locomotor activity. These experimeriments indicate that exposure to anxiogenic drugs increases accumbens dopamine activity, an effect that is consistent with other studies showing that the mesolimbic dopamine system is responsive to stressful stimuli. In addition, these results demonstrate that drug-induced increases in accumbens dopamine release are not unique to drugs of abuse.

Key words

Anxiogenic drugs Beta-CCE FG 7142 Dopamine Nucleus accumbens Stress Microdialysis 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Abercrombie EA, Keefe KA, DiFrischia DA, Zigmond MJ (1989) Differential effect of stress on in vivo dopamine release in striatum, nucleus accumbens and medial frontal cortex. J Neurochem 52:1655–1658PubMedGoogle Scholar
  2. Braestrup C, Nielsen M, Olsen CF (1980) Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of benzodiazepine receptors. Proc Natl Acad Sci USA 77:2288–2292PubMedGoogle Scholar
  3. Chen J, Paredes W, Li J, Smith D, Lowison J, Gardner EL (1990) Δ9-Tetrahydrocannabinol produces naloxone blockable enhancement of presynaptic basal dopamine efflux in nucleus accumbens of concious, freely-moving rats as measured by intracerebral microdialysis. Psychopharmacology 102:156–162Google Scholar
  4. Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E (1983) Beta-carbolines enhance shock-induced suppression of drinking in rats. Proc Natl Acad Sci USA 80:2072–2076PubMedGoogle Scholar
  5. D'Angio MD, Serrano A, Rivy JP, Scatton B (1987) Tail-pinch stress increases extracellular DOPAC levels (as measured by in vivo voltammetry) in rat nucleus accumbens but not frontal cortex: antagonism by diazepam and zolpidem. Brain Res 409:169–174CrossRefPubMedGoogle Scholar
  6. D'Angio MD, Serrano A, Scatton B (1990) Mesocorticolimbic dopaminergic systems and emotional states. J Neurosci Methods 34:135–142CrossRefPubMedGoogle Scholar
  7. Di Chiara G, Imperato A (1986) Preferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol, and barbiturates: studies with transcerebral dialysis in freely moving rats. Ann NY Acad Sci 473:367–381PubMedGoogle Scholar
  8. DiScala G, Sandner G (1989) Conditioned place aversion produced by FG 7142 is attenuated by haloperidol. Psychopharmacology 99:176–180CrossRefPubMedGoogle Scholar
  9. Dorow R, Horowski R, Paschelke G, Amin M, Braestrup C (1983) Severe anxiety induced by FG-7142, a beta-carboline ligand for benzodiazepine receptors. Lancet ii:98–99CrossRefGoogle Scholar
  10. Fada F, Argiolas A, Melis MR, Tissari AH, Onali PC, Gessa GL (1978) Stress-induced increase in 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the cerebral cortex and in nucleus accumbens: reversal by diazepam. Life Sci 23:2219–2224CrossRefGoogle Scholar
  11. Finlay JM, Damsma G, Fibiger JC (1992) Benzodiazepine-induced decreases in extracellular concentrations of dopamine in the nucleus accumbens after acute and repeated administration. Psychopharmacology 106:202–208PubMedGoogle Scholar
  12. Hernandez L, Hoebel BG (1988) Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci 42:1705–1712CrossRefPubMedGoogle Scholar
  13. Imperato A, Angelucci L, Casolini P, Zocchi A, Puglisi-Allegra S (1992) Repeated stressful experiences differently affect limbic dopamine release during and following stress. Brain Res 577:194–199CrossRefPubMedGoogle Scholar
  14. Keppel G (1982) Design and analysis: a researcher handbook. Prentiss-Hall, Englewood Cliffs, NJGoogle Scholar
  15. Leidenheimer NJ, Schecter MD (1988) Discriminative stimulus control by the anxiogenic beta-carboline FG-7142: generalization to a physiological stressor. Pharmacol Biochem Behav 30:351–355CrossRefPubMedGoogle Scholar
  16. McCullough LD, Salamone JD (1992a) Increases in extracellular dopamine levels and locomotor activity after direct infusion of phencyclidine into the nucleus accumbens. Brain Res 577:1–9CrossRefPubMedGoogle Scholar
  17. McCullough LD, Salamone JD (1992b) Involvement of nucleus accumbens dopamine in the motor activity induced by periodic food presentation: a microdialysis and behavioral study. Brain Res (in press)Google Scholar
  18. Moghadamm B, Roth RH, Bunney BS (1990) Characterization of dopamine release in the rat medial prefrontal cortex as assessed by in vivo microdialysis: comparison to the striatum. Neurosci 36:669–676CrossRefGoogle Scholar
  19. Ongini E, Barzaghi C, Marzanatti M (1983) Intrinsic and antagonistic effects of beta-carboline FG-7142 on behavioral and EEG actions of benzodiazepines and pentobarbital in cats. Eur J Pharmacol 95:125–129CrossRefPubMedGoogle Scholar
  20. Petersen E, Jensen LH (1984) Proconflict effect of benzodiazepine inverse agonists and other inhibitors of GABA function. Eur J Pharmacol 103:91–97CrossRefPubMedGoogle Scholar
  21. Salamone JD (1991) Behavioral pharmacology of dopamine systems: a new synthesis. In: Willner P, Scheel-Kruger J (eds) The mesolimbic dopamine system: from motivation to action. Cambridge University Press, Cambridge, England, pp 599–613Google Scholar
  22. Salamone JD (1992) Complex motor and sensorimotor functions of striatal and accumbens dopamine: involvement in instrumental behavior processes. Psychopharmacology 2:160–174Google Scholar
  23. Stutzmann JM, Bohme GA, Cochon M, Roux M, Blanchard JC (1987) Pro-conflict and electrocorticographic effects of drugs modulating GABA-ergic neurotransmission. Psychopharmacology 91:74–79CrossRefPubMedGoogle Scholar
  24. Takada K, Winger G, Cook J, Larscheid P, Woods J (1986) Discriminative and aversive properties of beta-carboline-3-carboxylic acid ethyl ester, a benzodiazepine receptor inverse agonist, in rhesus monkeys. Life Sci 38:1049–1056CrossRefPubMedGoogle Scholar
  25. Thierry AM, Tassin JP, Blanc G, Glowinski J (1976) Selective activation of mesocortical dopaminergic system by stress. Nature 263:242–244CrossRefPubMedGoogle Scholar
  26. Wise RA (1982) Neuroleptics and operant behavior: the anhedonia hypothesis. Behav Brain Sci 5:39–87Google Scholar
  27. Wise RA (1985) The anhedonia hypothesis: mark III. Behav Brain Sci 8:178–186Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • L. D. McCullough
    • 1
  • J. D. Salamone
    • 1
  1. 1.Department of PsychologyUniversity of ConnecticutStorrsUSA

Personalised recommendations