Skip to main content
Log in

Baclofen disrupts passive avoidance retention in rats

  • Original Investigations
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Baclofen (Lioresal, Ciba-Geigy) is an analog of the inhibitory neurotransmitter GABA and is used clinically to control spasticity. Recent studies have demonstrated that this compound produces a marked inhibition of synaptically evoked responses in area CA3 of the hippocampal slice, suggesting that this drug could influence behavior mediated by the limbic system. In the present study, male rats of the Fischer-344 strain were trained on a one-trial passive avoidance task and tested for retention 1 week later. After the training trial, separate groups of rats received either 5 or 10 mg/kg/4 ml IP of baclofen or the distilled H2O vehicle immediately, 10 min, or 60 min after training. One week later, the rats that received baclofen immediately after training reentered the test chamber with a significantly higher frequency than controls, although no differences in vacillatory responses were observed between groups. Similar effects were observed following posttrial administration of chlordiazepoxide. In a separate experiment rats were tested for locomotor activity after receiving the same doses of baclofen. Although baclofen decreased activity during a 30-min period after dosing, rats exposed to baclofen showed no significant change in activity relative to controls 1 week later. These data are consistent with the interpretation that baclofen may interfere with memory consolidation or retention.

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

Access this article

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Ault B, Evans R (1981) The depressant action of baclofen on the isolated spinal cord of the neonatal rat. Eur J Pharmacol 71:357–364

    Google Scholar 

  • Ault B, Nadler JV (1982) Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice. J Pharmacol Exp Ther 223:291–297

    Google Scholar 

  • Ault B, Nadler JV (1983) Anticonvulsant-like actions of baclofen in the rat hippocampal slice. Br J Pharmacol 78:701–708

    Google Scholar 

  • Baudry M, Oliver M, Creager P, Wieraszko A, Lynch G (1980) Increase in glutamate receptors following repetitave electrical stimulation in hippocampal slices. Life Sci 27:325–330

    Google Scholar 

  • Blaxter T, Carlen P (1985) Pre- and postsynaptic effects of baclofen in the rat hippocampal slice. Brain Res 341:195–199

    Google Scholar 

  • Bowery N (1982) Baclofen: 10 years on. TIPS 3:400–403

    Google Scholar 

  • Bowery N, Hill D, Hudson A, Doble A, Middlemiss D, Shaw J, Turnbull M (1980) (-)Baclofen decreases neurotransmitter release in the mammalian CNS by action at a novel GABA receptor. Nature 283:92–94

    Google Scholar 

  • Chung Shin-Ho (1977) Synaptic memory in the hippocampus. Nature 266:677–678

    Google Scholar 

  • Collins G, Anson J, Kelly E (1982) Baclofen: Effects on evoked field potentials and amino acid neurotransmitter release in the rat olfactory cortex slide. Brain Res 238:371–383

    Google Scholar 

  • Davidoff R, Sears E (1974) The effects of liorseal on synaptic activity in the isolated spinal cord. Neurology 24:957–963

    Google Scholar 

  • Desarmenien M, Feltz P, Ochipinti G, Santangelo F, Schlichter R (1984) Coexistence of GABAa and GABAb receptors on Ao and C primary afferents. Br J Pharmacol 81:327–333

    Google Scholar 

  • Dunlap K (1984) Functional and pharmacological differences between two types of GABA receptor on embryonic chick sensory neurons. Neurosci Lett 47:265–270

    Google Scholar 

  • Fagni L, Baudry M, Lynch G (1983) Classification and properties of acidic amino acid receptors in hippocampus. J Neurosci 3:1538–1546

    Google Scholar 

  • Fox S, Krnjevic K, Morris M, Puil E, Werman R (1978) Action of baclofen on mammalian synaptic transmission. Neuroscience 3:495–515

    Google Scholar 

  • Gold P, McGaugh J (1977) Hormones and memory. In: Miller L, Sandman C, Kastin A (eds) Neuropeptide influences on the brain and behavior. Raven, New York, pp 127–143

    Google Scholar 

  • Gray J, McNaughton N (1983) Comparison between the behavioral effects of septal and hippocampal lesions: A review. Neurosci Biobehav Rev 7:119–188

    Google Scholar 

  • Gruenthal M, Ault B, Armstrong D, Nadler JV (1984) Baclofen blocks kainic acid-induced epileptiform activity. Soc Neurosci Abstr 10:184

    Google Scholar 

  • Hill D, Bowery N (1981) 3H-baclofen and 3H-GABA bind to bicuculline-insensitive GABAb sites in rat brain. Nature 290:149–152

    CAS  PubMed  Google Scholar 

  • Jarvik M, Kopp R (1967) An improved passive avoidance learning situation. Psychol Rep 21:221–224

    Google Scholar 

  • Johnson F (1969) The effect of chlorpromazine on the decay and consolidation of short-term memory traces in mice. Psychopharmacology 16:105–114

    Google Scholar 

  • Knutsson E, Lindblom U, Martensson A (1974) Plasma and CSF levels of baclofen at optimal therapeutic responses in spastic paresis. J Neurol Sci 23:473–484

    Google Scholar 

  • Lidsky A, Slotnick B (1971) Effects of post-trial limbic stimulation on retention of a one-trial passive avoidance response. J Comp Physiol Psychol 76:337–348

    Google Scholar 

  • Mactutus C, Unger K, Tilson HA (1982) Neonatal chlordecone exposure impairs early learning and memory in the rat on a multiple measure passive avoidance task. Neurotoxicology 3:27–44

    Google Scholar 

  • McGaugh J (1983) Hormonal influences on memory. Annu Rev Psychol 34:297–323

    Google Scholar 

  • Newberry N, Nicoll R (1984) Direct hyperpolarizing action of baclofen on hippocampal pyramidal cells. Nature 308:450–452

    Google Scholar 

  • Newberry N, Nicoll R (1985) Comparison of the action of baclofen with GABA on rat hippocampal cells in vitro. J Physiol 360:161–185

    Google Scholar 

  • Oishi H, Iwahara S, Yang K, Yogi A (1972) Effects of chlordiazepoxide on passive avoidance responses in rats. Psychopharmacology 23:373–385

    Google Scholar 

  • Olpe H, Baudry M, Fagni L, Lynch G (1982) The blocking action of baclofen on excitatory transmission in the rat hippocampal slice. J Neurosci 2:698–703

    Google Scholar 

  • Pare W (1961) The effect of caffein and secanol on a visual discrimination task. J Comp Physiol Psychol 54:506–509

    Google Scholar 

  • Sandyk R, Gillman MA (1985) Baclofen-induced memory impairment. Clin Neuropharmacol 8:294–295

    Google Scholar 

  • Schlosser W, Franco S (1979) Modification of GABA-mediated depolarization of the cat ganglion by pentobarbital and two benzodiazepines. Neuropharmacology 18:377–381

    Google Scholar 

  • Siegel S (1956) Non-parametric statistics. McGraw-Hill, New York

    Google Scholar 

  • Steinberg H, Tomkiewicz M (1968) Drugs and memory. In: Efron DH (ed) Psychopharmacology: A review of progress 1957–1967. PHS publication # 1836. Washington, US Printing Office

    Google Scholar 

  • Swanson L, Teyler T, Thompson R (1982) Hippocampal long-term potentiation: Mechansims and implications for memory. Neurosciences Research Program Bulletin, vol. 20, no. 5, MIT Press

  • Swartzwelder HS, Sutch C, Bragdon A, Wilson WA (1985) Inhibition of epileptiform activity in hippocampal area CA3 by baclofen. Soc Neurosci Abstr

  • Swartzwelder HS, Bragdon A, Sutch C, Ault B, Wilson WA (1986) Baclofen suppresses hippocampal epileptiform activity at low concentrations without suppressing synaptic transmission. J Pharmacol Exp Ther 237:881–887

    MathSciNet  MATH  Google Scholar 

  • Tsuchiya T, Fukushima H (1978) Effects of benzodiazepines and pentobarbitone on the GABA-ergic recurrent inhibition of neurons. Eur J Pharmacol 48:421–424

    Google Scholar 

  • Valdes F, Fanelli R, McNamara J (1981) Barbiturate and GABA receptors coupled to benzodiazepine receptors in rat hippocampal formation: A radiohistochemical study. Life Sci 29:1895–1900

    Google Scholar 

  • Walsh T, Gallagher M, Bostock E, Dyer RS (1982) Trimethyltin impairs retention of a passive avoidance task. Neurobehav Toxicol Teratol 4:163–167

    Google Scholar 

  • Walsh T, Schulz D, Tilson H, Schmechel D (1986) Behavioral effects following colchicine-induced loss of granule cells in the dentate gyrus. Brain Res (in press)

  • Wierasko A (1983) Glutamic and aspartic acid as putative neurotransmitters: release and uptake studies on hippocampal slices. In: Seifert W (ed) Neurobiology of the hippocampus. Academic, New York, pp 175–196

    Google Scholar 

  • Winer B (1971) Statistical Principles in experimental design. McGraw-Hill, New York

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Swartzwelder, H.S., Tilson, H.A., McLamb, R.L. et al. Baclofen disrupts passive avoidance retention in rats. Psychopharmacology 92, 398–401 (1987). https://doi.org/10.1007/BF00210851

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00210851

Key words

Navigation