Skip to main content
SpringerLink
Log in

Kindling modifies morphine, cocaine and ethanol place preference

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Brailowsky and Garcia (1999) proposed the existence of a relationship between epilepsy and addiction. To prove this hypothesis, pentylenetetrazol kindled rats were tested in the conditioned place preference (CPP) paradigm for their reaction to various addictive drugs with different modes of action (morphine, cocaine and ethanol). In separate experiments, locomotor activity and body temperature after application of the same drugs were tested in kindled and non-kindled rats. In the CPP experiment there were significant differences between both groups of rats. Non-kindled animals showed place preference to morphine (5.0 mg/kg) or cocaine (20.0 mg/kg). This reaction was abolished in the kindled rats. Moreover, control rats demonstrated aversion to 2.0 g/kg ethanol. However, ethanol aversion was not detectable in kindled rats. Moreover, there was no difference between non-kindled and kindled rats in locomotor activity and body temperature after morphine (1.0 and 5.0 mg/kg), cocaine (10.0 and 20.0 mg/kg), or ethanol (0.5 and 2.0 g/kg) application. This suggests alterations in reward systems as a consequence of kindling. It is hypothesised that GABAergic neurones in the ventral tegmental area might play a major role in the alterations found.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Alderson HL, Jenkins TA, Kozak R, Latimer MP, Winn P (2001) The effects of excitotoxic lesions of the pedunculopontine tegmental nucleus on conditioned place preference to 4%, 12% and 20% sucrose solutions. Brain Res Bull 56:599–605

    Article  PubMed  CAS  Google Scholar 

  • Bardo MT (1998) Neuropharmacological mechanisms of drug reward: beyond dopamine in the nucleus accumbens. Crit Rev Neurobiol 12:37–67

    PubMed  CAS  Google Scholar 

  • Bartoletti M, Gaiardi M, Gubellini C, Bacchi A, Babbini M (1990) Morphine attenuation of a conditioned emotional response in post-dependent rats. Eur J Pharmacol 185:163–167

    Article  PubMed  CAS  Google Scholar 

  • Becker A, Grecksch G, Rüthrich H-L, Pohle W, Marx B, Matthies H (1992) Kindling and its consequences on learning in rats. Behav Neural Biol 57:37–43

    Article  PubMed  CAS  Google Scholar 

  • Becker A, Grecksch G, Matthies H (1994) The influence of diazepam on learning processes impaired by pentylenetetrazol. Naunyn-Schmiedeberg’s Arch Pharmacol 349:492–496

    Article  PubMed  CAS  Google Scholar 

  • Becker A, Grecksch G, Brosz M (1995) Antiepileptic drugs–their effects on kindled seizures and kindling-induced learning impairments. Pharmacol Biochem Behav 52:453–459

    Article  PubMed  CAS  Google Scholar 

  • Becker A, Grecksch G, Thiemann W, Höllt V (2000) Pentylenetetrazol-kindling modulates stimulated dopamine release in the nucleus accumbens of rats. Pharmacol Biochem Behav 66:425–428

    Article  PubMed  CAS  Google Scholar 

  • Blanchard DC, Weatherspoon A, Shepherd J, Rodgers RJ, Weiss SM, Blanchard RJ (1991) “Paradoxical" effects of morphine on antipredator defense reactions in wild and laboratory rats. Pharmacol Biochem Behav 40:819–828

    Article  PubMed  CAS  Google Scholar 

  • Brailowsky S, Garcia O (1999) Ethanol, GABA and epilepsy. Arch Med Res 30:3–9

    Article  PubMed  CAS  Google Scholar 

  • Carr GD, Fibiger HC, Phillips AG (1989) Conditioned place preference as a measure of drug reward. In: Liebmann JM, Cooper S (eds) The neuropharmacological basis of reward. Clarendon, Oxford, pp 264–319

    Google Scholar 

  • Chang L, Cloak CC, Ernst T (2003) Magnetic resonance spectroscopy studies of GABA in neuropsychiatric disorders. J Clin Psychiatry 64(Suppl 3):7–14

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Corda MG, Orlandi M, Lecca D, Carboni G, Frau V, Giorgi O (1991) Pentylenetetrazol-induced kindling in rats: effect of GABA function inhibitors. Pharmacol Biochem Behav 40:329–333

    Article  PubMed  CAS  Google Scholar 

  • Craft RM, Howard JL, Pollard GT (1988) Conditioned defensive burying as a model for identifying anxiolytics. Pharmacol Biochem Behav 30:775–780

    Article  PubMed  CAS  Google Scholar 

  • Cunningham CL, Henderson CM (2000) Ethanol-induced conditioned place aversion in mice. Behav Pharmacol 11:591–602

    PubMed  CAS  Google Scholar 

  • Di Chiara G (2002) Nucleus accumbens shell and core dopamine: differential role in behavior and addiction. Behav Brain Res 137:75–114

    Article  PubMed  CAS  Google Scholar 

  • File SE, Mabbutt PS, Becker A, Gonzalez LE, Fluck E (1996) Short-term rebound anxiolytic effects and long-term changes in platelet benzodiazepine binding after pentylenetetrazole-kindling in two strains of rat. Anxiety 2:109–116

    Article  PubMed  CAS  Google Scholar 

  • Fritschy JM, Kiener T, Bouilleret V, Loup F (1999) GABAergic neurons and GABA(A)-receptors in temporal lobe epilepsy. Neurochem Int 34:435–445

    Article  PubMed  CAS  Google Scholar 

  • Fujimori S, Yoneda Y (2004) Neuropsychiatric disorders and GABA. Nihon Shinkei Seishin Yakurigaku Zasshi 24:265–271

    PubMed  CAS  Google Scholar 

  • Genkova-Papazova MG, Petkova B, Shishkova N, Lazarova-Bakarova M (2001) Effect of the calcium channel blockers nifedipine and diltiazem on pentylenetetrazole kindling-provoked amnesia in rats. Eur Neuropsychopharmacol 11:91–96

    Article  PubMed  CAS  Google Scholar 

  • Gordon E, Devinsky O (2001) Alcohol and marijuana: effects on epilepsy and use by patients with epilepsy. Epilepsia 42:1266–1272

    Article  PubMed  CAS  Google Scholar 

  • Kokkinidis L, Borowski TB (1991) Sensitization of mesolimbic brain stimulation reward after electrical kindling of the amygdala. Brain Res Bull 27:791–796

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Koob GF (2000) Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci 909:170–185

    Article  PubMed  CAS  Google Scholar 

  • Lamberty Y, Klitgaard H (2000) Consequences of pentylenetetrazole kindling on spatial memory and emotional responding in the rat. Epilepsy Behav 1:256–261

    Article  PubMed  Google Scholar 

  • Linseman MA, Cottrell G, Burnham WM (1994) Decreased voluntary ethanol selection in amygdala-kindled rats. Pharmacol Biochem Behav 48:31–36

    Article  PubMed  CAS  Google Scholar 

  • Luthman J, Humpel C (1997) Pentylenetetrazol kindling decreases N-methyl-D-aspartate and kainate but increases gamma-aminobutyric acid-A receptor binding in discrete rat brain areas. Neurosci Lett 239:9–12

    Article  PubMed  CAS  Google Scholar 

  • Maldonado C, Rodri, guez-Arias M, Aguilar MA, Minarro J (2003) GHB differentially affects morphine actions on motor activity and social behaviours in male mice. Pharmacol Biochem Behav 76:259–265

    Article  PubMed  CAS  Google Scholar 

  • McBride WJ, Murphy JM, Ikemoto S (1999) Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res 101:129–152

    Article  PubMed  CAS  Google Scholar 

  • McNamara JO, Bonhaus DW, Shin DW, Crain BJ, Gellman RL, Giacchino JL (1986) The kindling model of epilepsy: a critical review. Crit Rev Neurobiol 1:341–391

    Google Scholar 

  • Meldrum BS (1989) GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br J Clin Pharmacol 27(Suppl 1):S3–S11

    Google Scholar 

  • Meldrum BS (1995) Neurotransmission in epilepsy. Epilepsia 36(Suppl 1):S30–S35

    Article  Google Scholar 

  • Metz GA, Gonzalez CL, Piecharka DM, Whishaw IQ (2003) Acute alcohol administration improves skilled reaching success in intact but not 6-OHDA dopamine depleted rats: a subsystems analysis of the motoric and anxiolytic effects of alcohol. Behav Brain Res 142:167–174

    Article  PubMed  CAS  Google Scholar 

  • Paine TA, Jackman SL, Olmstead MC (2002) Cocaine-induced anxiety: alleviation by diazepam, but not buspirone, dimenhydrinate or diphenhydramine. Behav Pharmacol 13:511–523

    PubMed  CAS  Google Scholar 

  • Paredes RG, Muzzi G, Aguirre E, Romero V (2000) Can a generalized kindling seizure induce a reward state? Epilepsy Res 38:249–257

    Article  PubMed  CAS  Google Scholar 

  • Rauca C, Pohle W, Grunenberg K, Franze S (2000) Hypothermia inhibits pentylenetetrazol kindling and prevents kindling-induced deficit in shuttle-box avoidance. Pharmacol Biochem Behav 65:23–30

    Article  PubMed  CAS  Google Scholar 

  • Raven MA, Necessary BD, Danluck DA, Ettenberg A (2000) Comparison of the reinforcing and anxiogenic effects of intravenous cocaine and cocaethylene. Exp Clin Psychopharmacol 8:117–124

    Article  PubMed  CAS  Google Scholar 

  • Schmutz M (1987) Relevance of kindling and related processes to human epileptogenesis. Prog Neuro-Psychopharmacol 11:505–525

    Article  CAS  Google Scholar 

  • Sejima H, Ito M, Kishi K, Tsuda H, Shiraishi H (1997) Regional excitatory and inhibitory amino acid concentrations in pentylenetetrazol kindling and kindled rat brain. Brain Dev 19:171–175

    Article  PubMed  CAS  Google Scholar 

  • Shippenberg TS, Koob GF (2002) Recent advances in animal models of drug addiction. Lippincott, Williams & Witkins, Washington, Philadelphia, pp 1381–1398

    Google Scholar 

  • Spanagel R, Weiss F (1999) The dopamine hypothesis of reward: past and current status. Trends Neurosci 22:521–527

    Article  PubMed  CAS  Google Scholar 

  • Vayer P, Mandel P, Maitre M (1987) Gamma-hydroxybutyrate, a possible neurotransmitter. Life Sci 41:1547–1557

    Article  PubMed  CAS  Google Scholar 

  • Voigt JP, Morgenstern E (1990) Pentylenetetrazole kindling impairs learning in mice. Biomed Biochim Acta 49:143–145

    PubMed  CAS  Google Scholar 

  • Wilson MA, Burghardt PR, Ford KA, Wilkinson MB, Primeaux SD (2004) Anxiolytic effects of diazepam and ethanol in two behavioral models: comparison of males and females. Pharmacol Biochem Behav 78:445–458

    Article  PubMed  CAS  Google Scholar 

  • Xi ZX, Stein EA (2002) GABAergic mechanisms of opiate reinforcement. Alcohol Alcohol 37:485–494

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

We gratefully acknowledge the expert assistance of Ms. P. Dehmel, Ms. R. Domm, Ms. C. Knape and Ms. G. Schulze. We thank Mr. A. K. Toms (UK) for help in improving the English.

Author information

Authors and Affiliations

  1. Institute of Pharmacology and Toxicology, Otto-von-Guericke University, Faculty of Medicine, Leipziger Str. 44, 39120, Magdeburg, Germany

    Axel Becker, Marco Schmitz & Gisela Grecksch

Authors
  1. Axel Becker
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marco Schmitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Gisela Grecksch
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Axel Becker.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Becker, A., Schmitz, M. & Grecksch, G. Kindling modifies morphine, cocaine and ethanol place preference. Exp Brain Res 168, 33–40 (2006). https://doi.org/10.1007/s00221-005-0081-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-005-0081-3

Keywords

Search

Navigation