Skip to main content
Log in

Dose-dependent effects of the D3-preferring agonist 7-OH-DPAT on motor behaviors and place conditioning

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

Abstract

Dose-dependent effects of 7-OH-DPAT on several behaviors, including place preference, were assessed. Three 2-day conditioning trials were conducted. On 1 day, animals received an injection of one of eight doses of 7-OH-DPAT (0–5 mg/kg) and were placed into a distinct compartment for 40 min. On the other day, animals received an injection of saline and were placed into a different compartment for 40 min. Locomotion, sniffing, and yawning were measured following the first and last injection of 7-OH-DPAT. Place conditioning was assessed on the day following the last trial. 7-OH-DPAT produced a U-shaped dose-dependent change in locomotion and sniffing, and an inverted U-shaped dose-dependent change in yawning. Additionally, repeated administration of 0.1 mg/kg sensitized yawning, whereas 5 mg/kg sensitized locomotion. None of the doses of 7-OH-DPAT produced conditioned place preference, however, there was a trend for conditioned place aversion at 0.03 mg/kg. By contrast, LiCl (127 mg/kg) produced conditioned place aversion and amphetamine (1 mg/kg) produced conditioned place preference using the same conditioning parameters. A subsequent experiment in which the number of animals and conditioning trials were increased demonstrated that the 0.03 mg/kg dose of 7-OH-DPAT produced conditioned place aversion. 7-OH-DPAT has a higher affinity for D3 receptors relative to D2 receptors. Therefore, it is suggested that intermediate doses (0.01–0.1 mg/kg) that increase yawning, and decrease locomotion and sniffing, may preferentially occupy D3 receptors. Furthermore, the results suggest that these putative D3-preferring doses have weak aversive effects.

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

Access this article

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

  • Booth RG, Baldessarini RJ, Marsh E, Owens CE (1994) Actions of (+)-7-hydroxy-N-N-dipropylaminotetralin (7-OH-DPAT) on dopamine synthesis in limbic and extrapyramidal regions of rat brain. Brain Res 662:283–288

    Article  PubMed  Google Scholar 

  • Caine SB, Koob GF (1993) Modulation of cocaine self-administration in the rat through D-3 dopamine receptors. Science 260:1814–1816

    PubMed  Google Scholar 

  • Carlsson A (1975) Receptor-mediated control of dopamine metabolism. In: Usdin E, Synder S (eds) Pre- and postsynaptic receptors. Dekker, New York pp 49–63

    Google Scholar 

  • Daly SA, Waddington JL (1993) Behavioural effects of the putative D-3 dopamine receptor agonist 7-OH-DPAT in relation to other “D-2-like” agonists. Neuropharmacology 32:509–510

    Article  PubMed  Google Scholar 

  • Damsma G, Bottema T, Westerink BHC, Tepper PT, Dijkstra D, Pugsley TA, Mackenzie RG, Heffner TG, Wikström H (1993) Pharmacological aspects ofR-(+)-7-OH- DPAT, a putative dopamine D3 receptor ligand. Eur J Pharmacol 249:R9-R10

    Article  PubMed  Google Scholar 

  • De Fonseca FR, Rubio P, Martín-Calderón JL, Caine SB, Koob GF, Navarro M (1995) The dopamine receptor agonist 7-OH-DPAT modulates the acquisition and expression of morphine-induced place preference. Eur J Pharmacol 274:47–55

    Article  PubMed  Google Scholar 

  • Hoffman DC (1989) The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Res Bull 23:373–387

    Article  PubMed  Google Scholar 

  • Hoffman DC, Beninger RJ (1989) The effects of selective dopamine D1 or D2 receptor antagonists on the establishment of agonist-induced place conditioning in rats. Pharmacol Biochem Behav 33:273–279

    Article  PubMed  Google Scholar 

  • Kostrzewa RM, Brus R, Rykaczewska M, Plech A (1993) Lowdose quinpirole ontogenically sensitizes to quinpirole-induced yawning in rats. Pharmacol Biochem Behav 44:487–489

    Article  PubMed  Google Scholar 

  • Lévesque D, Diaz J, Pilon C, Martres M, Giros B, Souil E, Schott D, Morgat J, Schwartz J, Sokoloff P (1992) Identification, characterization, and localization of the dopamine D3 receptor in rat brain using 7-[3H]hydroxy-N,N-di-n-propyl-2-aminotetralin. Proc Natl Acad Sci USA 89:8155–8159

    PubMed  Google Scholar 

  • Mallet PE, Beninger RJ (1994) 7 OH-DPAT produces place conditioning in rats. Eur J Pharmacol 261:R5-R6

    PubMed  Google Scholar 

  • Mattingly BA, Rowlett JK, Lovell G (1993) Effects of daily SKF 38393, quinpirole, and SCH 22390 treatments on locomotor activity and subsequent sensitivity to apomorphine. Psychopharmacology 110:320–326

    Article  PubMed  Google Scholar 

  • McElroy JF (1994) Discriminative stimulus properties of 7-OH-DPAT, a dopamine D3-selective receptor ligand. Pharmacol Biochem Behav 48:531–3

    Article  PubMed  Google Scholar 

  • Neisewander JL, Lucki I, McGonigle P (1991) Behavioral and neurochemical effects of chronic administration of reserpine and SKF-39383 in rats. J Pharmacol Exp Ther 257:850–860

    PubMed  Google Scholar 

  • Sibley DR, Monsma JR (1992) Molecular biology of dopamine receptors. Trends Pharmacol Sci 13:61–69

    Article  PubMed  Google Scholar 

  • Sokoloff P, Giros B, Martres M, Bouthenet M, Schwartz J (1990) Molecular cloning and characterization of a novel dopamine receptor (D3) as a target for neuroleptics. Nature 347:146–151

    Article  PubMed  Google Scholar 

  • Svensson K, Carlsson A, Waters N (1994) Locomotor inhibition by the D3 ligandR-(+)-7-OH-DPAT is independent of changes in dopamine release. J Neural Transm 95:71–74

    Article  PubMed  Google Scholar 

  • Van den Buuse M (1993) Effects of 7-hydroxy-N,N-di-n-propylaminotetralin on behaviour and blood pressure of spontaneously hypertensive rats. Eur J Pharmacol 243:169–77

    Article  PubMed  Google Scholar 

  • Waters N, Svensson K, Haadsma-Svensson SR, Smith MW, Carlsson A (1993) The dopamine D3-receptor: a postsynaptic receptor inhibitory on rat locomotor activity. J Neural Transm 94:11–19

    Article  Google Scholar 

  • White FJ, Hu XT, Brooderson RJ (1990) Repeated stimulation of dopamine D-1 receptors enhances the effects of dopamine receptor agonists. Eur J Pharmacol 191:497–499

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khroyan, T.V., Baker, D.A. & Neisewander, J.L. Dose-dependent effects of the D3-preferring agonist 7-OH-DPAT on motor behaviors and place conditioning. Psychopharmacology 122, 351–357 (1995). https://doi.org/10.1007/BF02246265

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246265

Key words

Navigation