Skip to main content
SpringerLink
Log in

Clorgyline-induced switch from locomotion to mouthing in sensitization to the dopamine D2/D3 agonist quinpirole in rats: role of sigma and imidazoline I2 receptors

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

Abstract

Rationale

The monoamine oxidase inhibitor (MAOI) clorgyline, blocks locomotor sensitization to the D2/D3 dopamine agonist quinpirole and sensitizes self-directed mouthing behavior in rats by a mechanism independent of MAO inhibition. Clorgyline has a high affinity for imidazoline I2 and sigma receptors, which could account for its effects on quinpirole sensitization.

Objectives

To examine whether the effect of clorgyline on quinpirole sensitization is attributed to stimulation of either I2 or sigma receptors.

Methods

In one experiment, rats received injections of the I2 receptor agonist 2-BFI (0.2 mg/kg, IP) or vehicle, 90 min prior to each injection of quinpirole (0.5 mg/kg, SC, × 8, twice weekly) or saline. A similar protocol was used to examine the effects of the MAOI Ro 41-1049 (10 mg/kg, SC) on quinpirole sensitization. Unlike clorgyline, Ro 41-1049 has no affinity for sigma or I2 sites. An initial experiment demonstrated that intermittent injections of clorgyline (1 mg/kg, SC) are as effective as a continuous clorgyline administration (1 mg/kg per day via osmotic mini-pump) on quinpirole sensitization.

Results

Like clorgyline, Ro 41-1049, but not 2-BFI, blocked the development of quinpirole-induced locomotor sensitization and induced instead sensitization of self-directed mouthing.

Conclusions

Because Ro 41-1049 produced the same effects as clorgyline, and 2-BFI had no effects on quinpirole sensitization, it is unlikely that clorgyline exerts its effects via an action at sigma or I2 receptors. Our results are consistent with the suggestion that clorgyline and Ro 41-1049 affect the behavioral response to quinpirole via the MAOI-displaceable quinpirole binding (MQB) site, and the hypothesis that the MQB site selects what motor output becomes sensitized to repeated injections of quinpirole.

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. A
Fig. 2. A
Fig. 3. A

Similar content being viewed by others

References

  • Alemany R, Olmos G, Garcia-Sevilla JA (1995) The effects of phenelzine and other monoamine oxidase inhibitor antidepressants on brain and liver I2 imidazoline preferring-receptors. Br J Pharmacol 114:837–845

    CAS  PubMed  Google Scholar 

  • Angrist B (1983) Psychosis induced by central nervous system stimulants and related drugs. In: Creese I (ed) Stimulants: neurochemical, behavioural and clinical perspectives. Raven Press, New York, pp 1–30

    Google Scholar 

  • Canadian Council on Animal Care (1993) Guide to the care and use of experimental animals, vol 1, 2nd edn. CCAC, Ottawa, Ontario

  • Clement H, Grote C, Wesemann W (1990) In vivo studies on the effect of monoamine oxidase inhibitors on dopamine and serotonin metabolism in rat brain areas. J Neural Transm Suppl 32:85–88

    CAS  PubMed  Google Scholar 

  • Colzi A, d'Agostini F, Kettler R, Borroni E, DaPrada M (1990) Effect of selective and reversible MAO inhibitors on dopamine outflow in rat striatum: a microdialysis study. J Neural Transm 32:79–84

    CAS  PubMed  Google Scholar 

  • Culver KE, Szechtman H (1997) Monoamine oxidase inhibitor sensitive site implicated in sensitization to quinpirole. Eur J Pharmacol 339:109–111

    Article  CAS  PubMed  Google Scholar 

  • Culver KE, Rosenfeld JM, Szechtman H (2000) A switch mechanism between locomotion and mouthing implicated in sensitization to quinpirole in rats. Psychopharmacology 151:202–210

    Google Scholar 

  • Culver KE, Rosenfeld JM, Szechtman H (2002) Monoamine oxidase inhibitor-induced blockade of locomotor sensitization to quinpirole: role of striatal dopamine uptake inhibition. Neuropharmacology 43:385–393

    Article  CAS  PubMed  Google Scholar 

  • Eilam D, Szechtman H (1989) Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur J Pharmacol 161:151–157

    CAS  PubMed  Google Scholar 

  • Eilam D, Talangbayan H, Canaran G, Szechtman H (1992) Dopaminergic control of locomotion, mouthing, snout contact, and grooming: opposing roles of D1 and D2 receptors. Psychopharmacology 106:447–454

    Google Scholar 

  • Greenshaw AJ (1986) Osmotic mini-pumps: a convenient program for weight adjusted filling concentrations. Brain Res Bull 16:759–761

    CAS  PubMed  Google Scholar 

  • Heeringa MJ, d'Agostini F, DeBoer P, DaPrada M, Damsma G (1997) Effect of monoamine oxidase A and B and of catechol-O-methyltransferase inhibition on L-DOPA-induced circling behaviour. J Neural Transm 104:593–603

    CAS  PubMed  Google Scholar 

  • Hirabayshi M, Okada S, Tadokoro S (1991) Comparison of sensitization to ambulation-increasing effects of cocaine and methamphetamine after repeated administration in mice. J Pharm Pharmacol 43:827–830

    CAS  PubMed  Google Scholar 

  • Hoffman DC, Wise RA (1992) Locomotor-activating effects of the D2 agonist bromocriptine show environment-specific sensitization following repeated injections. Psychopharmacology 107:277–284

    Google Scholar 

  • Hudson HL, Gough R, Tyacke R, Lione L, Lalies M, Lewis J, Husbands S, Knight P, Murray F, Hutson P, Hutt DJ (1999) Novel selective compounds for the investigation of imidazoline receptors. Ann NY Acad Sci 881:81–91

    CAS  PubMed  Google Scholar 

  • Itzhak Y, Kassim CO (1990) Clorgyline displaces high affinity for sigma binding sites in C57BL/6 mouse brain. Eur J Pharmacol 176:107–108

    Article  CAS  PubMed  Google Scholar 

  • Itzhak Y, Stein I, Zhang S, Kassim CO, Cristante D (1991) Binding of σ-ligands to C57BL/6 mouse brain membranes: effects of monoamine oxidase inhibitors and subcellular distribution studies suggest the existence of σ-receptor subtypes. J Pharmacol Exp Ther 257:141–148

    CAS  PubMed  Google Scholar 

  • Levant B, Grigoradis DE, DeSouza EB (1993) Monoamine oxidase inhibitors inhibit [3H]quinpirole binding in rat striatal membranes. Eur J Pharmacol 246:171–178

    CAS  PubMed  Google Scholar 

  • Levant B, Moehlenkamp JD, Morgan KA, Leonard NL, Cheng CC (1996) Modulation of [3H]quinpirole binding in brain by monoamine oxidase inhibitors: Evidence for a potential novel binding site. J Pharmacol Exp Ther 278:145–153

    Google Scholar 

  • Levant B, Morgan KA, Beckendorf-Ahlgren JA, Grandy DK, Chen K, Shih JC, Seif I (2001) Modulation of [3H]quinpirole binding at striatal D2 dopamine receptors by a monoamine oxidaseA-like site: evidence from radioligand binding studies and D2 receptor- and MAOA-deficient mice. Life Sci 70:229–241

    Article  CAS  PubMed  Google Scholar 

  • Lione LA, Nutt DJ, Hudson AL (1998) Characterization and localization of [3H]2-(2-benzofuranyl)-2-imidazoline binding in rat brain: a selective ligand for imidazoline I2 receptors. Eur J Pharmacol 353:123–135

    CAS  PubMed  Google Scholar 

  • Mattingly B, Gotsick S (1989) Conditioning and experimental factors affecting the development of sensitization to apomorphine. Behav Neurosci 103:1311–1317

    CAS  PubMed  Google Scholar 

  • Menkel M, Terry P, Pontecorvo M, Katz J, Witkin J (1991) Selective σ ligands block stimulant effects of cocaine. Eur J Pharmacol 201:251–252

    Article  CAS  PubMed  Google Scholar 

  • Nutt D, French N, Handley S, Hudson A, Husbands S, Jackson S, Jordan S, Lalies M, Lewis J, Lione L, Mallard N, Pratt J (1995) Functional studies of specific imidazoline-2 receptor ligands. Ann NY Acad Sci 763:125–129

    CAS  PubMed  Google Scholar 

  • Olmos G, Gabilondo A, Miralles A, Escriba P, Garcia-Sevilla E (1993) Chronic treatment with the monoamine oxidase inhibitors clorgyline and pargyline down-regulates non-adrenoceptor [3H]-idazoxan binding sites in the rat brain. Br J Pharmacol 108:597–603

    CAS  PubMed  Google Scholar 

  • Robinson TE, Becker JB (1986) Enduring change in brain and behavior produced by chronic amphetamine administration: a review and evaluation of animal models of amphetamine psychosis. Brain Res 396:157–198

    CAS  PubMed  Google Scholar 

  • Robinson TE, Berridge KC (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Rev 18:247–291

    CAS  PubMed  Google Scholar 

  • Sastre-Coll A, Esteban S, Miralles A, Zanetti R, Garcia-Sevilla J (2001) The imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline is a dopamine releasing agent in the rat striatum in vivo. Neurosci Lett 301:29–32

    Article  CAS  PubMed  Google Scholar 

  • Segal DS, Schuckit MA (1983) Animal models of stimulant-induced psychosis. In: Creese I (ed) Stimulants: neurochemical, behavioural and clinical perspectives. Raven Press, New York, pp 131–167

    Google Scholar 

  • Szechtman H, Dai H, Mustafa S, Einat H, Sullivan RM (1994a) Effects of dose and interdose interval on locomotor sensitization to the dopamine agonist quinpirole. Pharmacol Biochem Behav 48:921–928

    CAS  PubMed  Google Scholar 

  • Szechtman H, Talangbayan H, Canaran G, Dai H, Eilam D (1994b) Dynamics of behavioral sensitization induced by the dopamine agonist quinpirole and a proposed central energy mechanism. Psychopharmacology 115:95–104

    Google Scholar 

  • Szechtman H, Culver KE, Eilam D (1999) Role of dopamine systems in obsessive-compulsive disorder: implications from a novel psychostimulant-induced animal model. Pol J Pharmacol 51:55–61

    CAS  PubMed  Google Scholar 

  • Takahashi S, Miwa T, Horikomi K (2000) Involvement of σ1 receptors in methamphetamine-induced behavioral sensitization in rats. Neurosci Lett 289:21–24

    CAS  PubMed  Google Scholar 

  • Ujike H, Kanzaki A, Okumura K, Akiyama K, Otsuki S (1992a) Sigma antagonist BMY 14802 prevents methamphetamine-induced sensitization. Life Sci 50:129–134

    Google Scholar 

  • Ujike H, Okumura K, Zushi Y, Akiyama K, Otsuki S (1992b) Persistent supersensitivity of σ receptors develops during repeated methamphetamine treatment. Eur J Pharmacol 211:23–328

    Article  PubMed  Google Scholar 

  • Ujike H, Kuroda S, Otsuki S (1996) σ receptor antagonists block the development of sensitization to cocaine. Eur J Pharmacol 296:123–128

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Donna Waxman for help in carrying out a portion of the study. This study was supported by the Canadian Institutes of Health Research (MT-12852). H.S. is a Senior Research Fellow of the Ontario Mental Health Foundation.

Author information

Authors and Affiliations

  1. Department of Psychiatry and Behavioural Neurosciences, McMaster University, Health Science Center, Room 4N82, 1200 Main Street West, Hamilton, Ontario, Canada L8N 3Z5

    Kirsten E. Culver & Henry Szechtman

Authors
  1. Kirsten E. Culver
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Henry Szechtman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Henry Szechtman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Culver, K.E., Szechtman, H. Clorgyline-induced switch from locomotion to mouthing in sensitization to the dopamine D2/D3 agonist quinpirole in rats: role of sigma and imidazoline I2 receptors. Psychopharmacology 167, 211–218 (2003). https://doi.org/10.1007/s00213-003-1408-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-003-1408-z

Keywords

Search

Navigation