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Conditioned place aversion produced by FG 7142 is attenuated by haloperidol

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Abstract

A place conditioning paradigm was used to examine the affective properties of FG 7142, a benzodiazepine receptor inverse agonist. At the highest dose tested (10 mg/kg, IP), FG 7142 produced a significant place aversion to the drug-paired compartment. In a second experiment, haloperidol injections were given before FG 7142. It was found that haloperidol (0.2 mg/kg) significantly reduced the measured conditioned place aversion produced by FG 7142, without exhibiting any aversive or rewarding effects by itself. These results suggest that dopamine receptors are involved in the learning or expression of conditioned place aversion induced by benzodiazepine receptor inverse agonists.

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References

  1. Bardo MT, Miller JS, Neisewander JL (1984) Conditioned place preference with morphine: the effect of extinction training on the reinforcing CR. Pharmacol Biochem Behav 21:545–549

  2. Beninger RJ (1983) The role of dopamine in locomotor activity and learning. Brain Res Rev 6:173–196

  3. Braestrup C, Nielsen M, Honoré T, Jensen LH, Petersen EN (1983) Benzodiazepine receptor ligands with positive and negative efficacy. Neuropharmacology 22:1451–1457

  4. Brose N, O'Neill RD, Boutelle MG, Anderson SMP, Fillenz M (1987) Effects of an anxiogenic benzodiazepine receptor ligand on motor activity and dopamine release in nucleus accumbens and striatum. Neurosci 7:2917–2926

  5. Carr GD, White NM (1983) Conditioned place preference from intra-accumbens but not intra-caudate amphetamine injections. Life Sci 33:2551–2557

  6. Carr GD, Phillips AG, Fibiger HC (1988) Independence of amphetamine reward from locomotor stimulation demonstrated by conditioned place preference. Psychopharmacology 94:221–226

  7. Corda MG, Blaker WD, Mendelson WB, Guidotti A, Costa E (1983) β-carbolines enhance shock-induced suppression of drinking in rats. Proc Natl Acad Sci USA 80:2072–2076

  8. Costa E, Guidotti A (1979) Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol 19:531–545

  9. Depaulis A, Piret B, Vergnes M (1988) Effects of benzodiazepine receptors ligands on defensive and submissive behaviours in the rat. Psychopharmacology 96:S15

  10. Di Scala G, Martin-Iverson MT, Phillips AG, Fibiger HC (1985) The effects of progabide (SL 76002) on locomotor activity and conditioned place preference induced by d-amphetamine. Eur J Pharmacol 107:271–274

  11. Di Scala G, Rohmer JG, Sandner G (1988) Ethopharmacological study of the effects of anxiolytic and anxiogenic drugs in the conditioned burying paradigm. Role of the periaqueductal gray. Psychopharmacology 96:S16

  12. Di Scala G, Sandner G (1989) Conditioned place aversion produced by microinjections of semicarbazide into the periaqueductal gray of the rat. Brain Res 483:91–97

  13. Dixon WJ (1982) BMDP statistical software. University of California Press, Los Angeles

  14. Dorow R, Horowski R, Paschelke G, Amin M, Braestrub C (1983) Severe anxiety induced by FG 7142, a β-carboline ligand for benzodiazepine receptors. Lancet II:98–99

  15. Fadda F, Argiolas R, Melis MR, Tissari AH, Onali PL, 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 23:2219–2224

  16. File SE (1986) Aversive and appetitive properties of anxiogenic and anxiolytic agents. Behav Brain Res 21:189–194

  17. File SE, Pellow S, Braestrup C (1985) Effects of the β-carboline, FG 7142, in the social interaction test of anxiety and the hole-board: correlations between behaviour and plasma concentrations. Pharmacol Biochem Behav 22:941–944

  18. Jensen LH, Petersen EN, Honoré T, Drejer J (1986) Bidirectional modulation of GABA function by beta-carbolines. In: Biggio G, Costa E (eds) GABAergic transmission and anxiety. Raven Press, New York, pp 79–89

  19. Jensen LH, Stephens DN, Sarter M, Petersen EN (1987) Bidirectional effects of beta-carbolines and benzodiazepines on cognitive processes. Brain Res Bull 19:359–364

  20. Leidenheimer NJ, Schechter MD (1988) Discriminative stimulus control by the anxiogenic beta-carboline FG 7142: generalization to a physiological stressor. Pharmacol Biochem Behav 30:351–355

  21. Macdonald RL, Weddle MG, Gross RA (1986) Benzodiazepine, beta-carboline, and barbiturate actions on GABA responses. In: Biggio G, Costa E (eds) GABAergic transmission and anxiety. Raven Press, New York, pp 67–78

  22. Marescaux C, Vergnes M, Jensen LH, Petersen E, Depaulis A, Micheletti G, Warter JM (1987) Bidirectional effects of betacarbolines in rats with spontaneous petit-mal seizures. Brain Res Bull 19:327–335

  23. Mithani S, Martin-Iverson MT, Phillips AG, Fibiger HC (1986) The effects of haloperidol on amphetamine- and methylphenidate-induced conditioned place preferences and locomotor activity. Psychopharmacology 90:247–252

  24. Petersen EN, Jensen LH, Honoré T, Braestrup C (1983) Differential pharmacological effects of BZ receptor inverse agonists. In: Biggio G, Costa E (eds) Benzodiazepine recognition site ligands: biochemistry and pharmacology. Raven Press, New York, pp 57–64

  25. Pole P (1988) Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action. Prog Neurobiol 31:349–424

  26. Sato M, Ogawa T (1984) Abnormal behavior in epilepsy and catecholamines. In: Fariello RG, Morselli PL, Lloyd KG, Quesney LP, Engel J (eds) Neurotransmitter, seizures, and epilepsy. Raven Press, New York, pp 1–9

  27. Spyraki C, Fibiger HC (1988) A role for the mesolimbic dopamine system in the reinforcing properties of diazepam. Psychopharmacology 94:133–137

  28. Spyraki C, Fibiger HC, Phillips AG (1982a) Dopaminergic substrates of amphetamine-induced place preference conditioning. Brain Res 253:185–193

  29. Spyraki C, Fibiger HC, Phillips AG (1982b) Cocaine-induced place preference conditioning: lack of effects of neuroleptics and 6-hydroxydopamine lesions. Brain Res 253:195–203

  30. Spyraki C, Kazandjian A, Varonos D (1985) Diazepam-induced place preference conditioning: appetitive and antiaversive properties. Psychopharmacology 87:225–232

  31. Stephens DN, Kehr W, Duka T (1986) Anxiolytic and anxiogenic beta-carbolines: tools for the study of anxiety mechanisms. In: Biggio G, Costa E (eds) GABAergic transmission and anxiety. Raven Press, New York

  32. Tam SY, Roth RH (1985) Selective increase in dopamine metabolism in the prefrontal cortex by the anxiogenic β-carboline FG 7142. Biochem Pharmacol 34:1595–1598

  33. Wagner JA, Katz RJ (1984) Anxiogenic action of benzodiazepine antagonists Ro 15-1788 and CGS 8216 in the rat. Neurosci Lett 48:317–320

  34. Warter JM, Vergnes M, Depaulis A, Tranchant C, Rumbach L, Micheletti G, Marescaux C (1988) Effects of drugs affecting dopaminergic neurotransmission in rats with spontaneous petit mal-like seizures. Neuropharmacology 27:269–274

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Correspondence to Georges Di Scala.

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Di Scala, G., Sandner, G. Conditioned place aversion produced by FG 7142 is attenuated by haloperidol. Psychopharmacology 99, 176–180 (1989). https://doi.org/10.1007/BF00442804

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Key words

  • Place conditioning
  • Aversion
  • FG 7142
  • Haloperidol
  • Beta-carbolines