Psychopharmacology

, Volume 113, Issue 3–4, pp 422–428 | Cite as

Aversive properties of theκ opioid agonist U50,488 in the week-old rat pup

  • Gordon A. Barr
  • Shaoning Wang
  • Susan Carden
Original Investigations

Abstract

μ Opioids have been shown to produce analgesia and to be reinforcing during the first week of life in the rat. κ Opioids also have analgesic actions in both the infant and adult, but can be aversive in the mature animal. We examined the aversive effects of the κ opioid agonist U50,488 during the first postnatal week in the rat pup in three ways. In the first experiment, U50,488, injected peripherally (1.0–30.0 mg/kg), was paired with an odor and pups were tested 8 h later for positional preference for avoidance of that odor. This task is similar to conditioned preference/aversion tests used with adult animals. Both 3- and 7-day-old pups learned to avoid the odor adulterated side at the two higher doses. When exposed to odors previously associated with U50,488, pups at both ages decreased locomotor activity. In a second experiment, acute treatment with U50,488 increased ultrasonic distress vocalizations (USV) equally at 3 and 7 days of age, increased locomotor activity, and decreased rectal temperature. Neither of the latter two effects was correlated with the increase in USV production. The third experiment showed that conditioned odor cues increased USV 8 h later in 3- and 7-day-old pups at 1.0–10.0 mg/kg without changes in activity or rectal temperature. The results from these studies suggest that U50,488 can produce aversions in the neonatal rat pup as it does in the adult.

Key words

Opiates κ Opioids U50,488 Conditioned aversion Ultrasonic vocalization Distress vocalization Development Ontogeny 

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References

  1. Allerton CA, Smith JAM, Hunter JC, Hill RG, Hughes J (1989) Correlation of ontogeny with function of [3H]U69593 labelled kappa opioid binding sites in the rat spinal cord. Brain Res 502:149–157CrossRefPubMedGoogle Scholar
  2. Bals-Kubic B, Herz A, Shippenberg TS (1989) Evidence that the aversive effects of opioid antagonists and κ-agonists are centrally mediated. Psychopharmacology 98:203–206Google Scholar
  3. Barr GA (1992) The behavioral effects of opiates during development. In: Miller MW (ed) Development of the central nervous system: effects of alcohol and opiates. Wiley, New York, pp 221–254Google Scholar
  4. Barr GA (1993) Reinforcement properties of opiates during early development. In: Hammer RP Jr (ed) The neurobiology of opiates. CRC Press, Boca Raton, Fla, pp 63–83Google Scholar
  5. Barr GA, Rossi G (1992) Conditioned place preference produced by local injection of morphine into the ventral tegmental area of 3-day old rats. Dev Brain Res 66:133–136CrossRefGoogle Scholar
  6. Barr GA, Wang S (1992) Peripheral and central administration of cocaine produce conditioned odor preferences in the infant rat. Dev Brain Res 599:181–185Google Scholar
  7. Barr GA, Paredes W, Erickson KL, Zukin RS (1986) K-opioid receptor-mediated analgesia in the developing rat. Dev Brain Res 29:145–152CrossRefGoogle Scholar
  8. Bechara A, Kooy K van der (1987) Kappa receptors mediate the peripheral aversive effects of opiates. Pharmacol Biochem Behav 28:227–233Google Scholar
  9. Benton D (1988) The role of opiate mechanisms in social relationships. In: Lader MH (ed) The psychopharmacology of addiction. Oxford University Press, New York, pp 115–140Google Scholar
  10. Blumberg MS, Alberts JR (1990) Ultrasonic vocalizations by rat pups in the cold: an acoustic by-product of larynegeal braking? Behav Neurosci 104:808–817CrossRefPubMedGoogle Scholar
  11. Carden SE, Barr GA, Hofer MA (1991) Differential effects of specific opioid receptor agonists on rat pup isolation calls. Dev Brain Res 62:7–22CrossRefGoogle Scholar
  12. Carden SE, Bortot AT, Hofer MA (1993) Ultrasonic vocalizations are elicited from rat pups in the homecage by pentylenetetrazol and U50,488, but not naltrexone. Behav Neurosci (in press)Google Scholar
  13. DeCasper AJ, Fifer WP (1980) Of human bonding: newborns prefer their mothers' voices. Science 208:1174–1176Google Scholar
  14. DiChiara G, Imperato A (1988) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci 85:5274–5278PubMedGoogle Scholar
  15. Helmstetter FJ, Calcagnetti DJ, Cramer CP, Fanselow MS (1988) Ethylketocyclazocine and bremazocine analgesia in neonatal rats. Pharmacol Biochem Behav 30:817–821Google Scholar
  16. Hofer MA, Shair HN (1991) Independence of ultrasonic vocalization and thermogenic responses in infant rats. Behav Neurosci 105:41–48Google Scholar
  17. Hofer MA, Shair HN (1993) Ultrasonic vocalization, laryngeal braking and thermogenesis in rat pups: a reappraisal. Behav Neurosci 107:354–362Google Scholar
  18. Hoffman DC (1989) The use of place conditioning in studying the neuropharmacology of drug reinforcement. Brain Res Bull 23:373–387CrossRefPubMedGoogle Scholar
  19. Iwamoto ET (1986) Place-conditioning properties of mu, kappa and sigma opioid agonists. Alcohol Drug Res 6:327–339Google Scholar
  20. Jackson HC, Kitchen I (1989) Behavioural effects of selective μ-, κ-, and δ-opioid agonists in neonatal rats. Psychopharmacology 97:404–409Google Scholar
  21. Kehoe P, Blass EM (1986) Central nervous system mediation of positive and negative reinforcement in neonatal albino rats. Dev Brain Res 27:69–75CrossRefGoogle Scholar
  22. Kehoe P, Boylan C, Shoemaker W (1990) Differential effects of specific endogenous opioid systems on affective behaviors in neonatal rats. Neurosci Abstr 16:211Google Scholar
  23. Leslie FM, Loughlin S (1993) In: Hammer RP Jr (ed) The neurobiology of opiates. CRC Press, Boca Raton, Fla, pp 85–113Google Scholar
  24. McDowell J, Kitchen I (1987) Development of opioid systems: peptides receptors and pharmacology. Brain Res Rev 12:397–421CrossRefGoogle Scholar
  25. Mucha RF, Herz A (1985) Motivation properties of kappa and mu opioid receptor agonists studied with place and taste preference conditioning. Psychopharmacology 86:274–280CrossRefPubMedGoogle Scholar
  26. Panksepp J, Siviy S, Normansell L (1985) Brain opioids and social emotion. In: Reite M, Fields T (eds) The psychobiology of attachment and separation. Academic Press, New York, pp 3–49Google Scholar
  27. Pedersen PE, Blass EM (1982) Prenatal and postnatal determinants of the 1st suckling episode in albino rats. Dev Psychobiol 15:349–355CrossRefPubMedGoogle Scholar
  28. Rudy JW, Spear NE (1991) Tests of the ontogeny of learning and memory: issues, methods, and results. In: Shair HN, Barr GA, Hofer MA (eds) Developmental psychobiology: new methods and changing concepts. Oxford University Press, New York, pp 84–113Google Scholar
  29. Shippenberg TS, Herz A (1986) Differential effects of μ- and κ- opioid agonists on motivation processes. NIDA Res Monogr 75:563–566PubMedGoogle Scholar
  30. Smotherman WP (1982) Odor aversion learning by the rat fetus. Physiol Behav 29:769–771Google Scholar
  31. Spencer RL, Hruby VJ, Burks TF (1988) Body temperature response profiles for selective mu, delta and kappa opioid agonists in restrained and unrestrained rat. J Pharmacol Exp Ther 246:92–101PubMedGoogle Scholar
  32. Stickrod G, Kimble DP, Smotherman WP (1982) Met-enkephalin effects on associations formed in utero. Peptides 3:881–883CrossRefPubMedGoogle Scholar
  33. Winslow JT, Insel TR (1991) The infant rat separation paradigm: a novel test for novel anxiolytics. Trends Pharmacol Sci 12:402–404CrossRefPubMedGoogle Scholar
  34. Von Voightlander PF, Lahti RA, Ludens JH (1983) U50,488: selective and structurally novel non-mu (kappa) opioid agonist. J Pharmacol Exp Ther 224:7–12PubMedGoogle Scholar
  35. Yaksh TL (1986) The effects of intrathecally administered opioid and adrenergic agents on spinal function. In: Yaksh TL (ed) Spinal afferent processing. Plenum Press, New York, pp 165–195Google Scholar

Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • Gordon A. Barr
    • 1
    • 2
  • Shaoning Wang
    • 1
  • Susan Carden
    • 1
  1. 1.Department of Developmental PsychobiologyNew York State Psychiatric InstituteNew YorkUSA
  2. 2.Department of PsychologyHunter College of the City University of New YorkNew YorkUSA

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