Psychopharmacology

, Volume 104, Issue 1, pp 51–56 | Cite as

β-Endorphin-induced locomotor stimulation and reinforcement are associated with an increase in dopamine release in the nucleus accumbens

  • Rainer Spanagel
  • Albert Herz
  • Regine Bals-Kubik
  • Toni S. Shippenberg
Original Investigations

Abstract

In vivo microdialysis was used to compare the effects of β-endorphin upon dopamine (DA) release in the nucleus accumbens (NAC) of anesthetized versus freely moving rats, and to examine the role of the the mesolimbic DA system in mediating both the motoric and secondary reinforcing effects of this peptide. Microdialysis probes were inserted into the NAC and perfusates were analyzed for DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), using a reversed phase HPLC system with electrochemical detection for separation and quantification. Intracerebroventricular (ICV) administration of β-endorphin (2.5 and 5.0 µg) increased DA release and metabolites in both freely moving and anesthetized rats. This effect was of greater magnitude and duration in freely moving rats and was accompanied by stimulation of locomotor activity. The 5 µg dose also functioned as a secondary reinforcer in a conditioned place preference paradigm. A higher dose of β-endorphin (7.5 µg) stimulated DA release and metabolites in anesthetized rats but failed to affect these parameters in freely moving rats. At this dose, catalepsy and a loss of the reinforcing effects of this peptide were observed. These data demonstrate marked differences in the effects of β-endorphin upon DA release in the awake versus anesthetized rat. Further, the finding that the reinforcing and locomotor stimulating effects of β-endorphin only occur at those doses which stimulate DA release suggest that this action is critical for the expression of both behavioral effects.

Key words

Dopamine overflow/release Microdialysis Locomotor activity Reward Nucleus accumbens β-endorphin Intracerebroventricular/rat 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Amalric M, Cline EJ, Martinez JL, Bloom FE, Koob GF (1987) Rewarding properties of β-endorphin as measured by conditioned place preference. Psychopharmacology 91:14–20Google Scholar
  2. Bals-Kubik R, Herz A, Shippenberg TS (1988) β-endorphin-(1-27) is a naturally occurring antagonist of the reinforcing effects of opioids. Naunyn-Schmiedeberg's Arch Pharmacol 338:392–396Google Scholar
  3. Bannon MJ, Roth RH (1983) Pharmacology of mesocortical dopamine neurons. Pharmacol Rev 35:53–69Google Scholar
  4. Di Chiara G, Imperato A (1988a) Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats. J Pharmacol Exp Ther 244:1067–1078Google Scholar
  5. Di Chiara G, Imperato A (1988b) Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci USA 85:5274–5280Google Scholar
  6. Glick SD, Carlson JN, Baird JL, Maisonneuve IM, Bullock E (1988) Basal and amphetamine-induced asymmetries in striatal dopamine release and metabolism: bilateral in vivo microdialysis in normal rats. Brain Res 473:161–170Google Scholar
  7. Hernandez L, Hoebel BG (1988) Food reward and cocaine increase extracellular dopamine in the nucleus accumbens as measured by microdialysis. Life Sci 42:1705–1712Google Scholar
  8. Herz A, Shippenberg TS (1989) Neurochemical aspects of addiction: Opioids and other drugs of abuse. In: Goldstein A (ed) Molecular and cellular aspects of the drug addictions. Springer, New York Berlin Heidelberg, pp 111–141Google Scholar
  9. Iyengar S, Kim HS, Marien MR, McHugh D, Wood PL (1989) Modulation of mesolimbic dopaminergic projections by betaendorphin in the rat. Neuropharmacology 28:123–134Google Scholar
  10. Kalivas PW, Widerlöv E, Stanley D, Breese G, Prange AJ (1983) Enkephalin action on the mesolimbic system: a dopamine-dependent and a dopamine-independent increase in locomotor activity. J Pharmacol Exp Ther 227:229–237Google Scholar
  11. Kelley AE, Stinus L, Iverson SD (1980) Interaction betweend-Ala-Met-enkephalin, A10 dopaminergic neurons, and spontaneous behavior in the rat. Behav Brain Res 1:3–24Google Scholar
  12. Lohse M, Wuttke W (1981) Release and synthesis rates of catecholamines in hypothalamic, limbic and midbrain structures following intraventricular injections of beta-endorphin in male rats. Brain Res 229:389–398Google Scholar
  13. Mansour A, Khachaturian H, Lewis ME, Akil H, Watson JS (1988) Anatomy of CNS opioid receptors. Trends Neurosci 11:308–316Google Scholar
  14. Morgenson GJ (1987) Limbic-motor integration. Prog Psychobiol Physiol Psychol 12:117–170Google Scholar
  15. Paxinos G, Watson C (1982) The rat brain in stereotaxic coordinates. Academic Press, SydneyGoogle Scholar
  16. Phillipson OT, Griffiths AC (1985) The topographic order of inputs to nucleus accumbens in the rat. Neuroscience 16:275–286Google Scholar
  17. Pijnenburg AJJ, Honig WMM, van Rossum JM (1973) Stimulation of motor activity following injection of dopamine into the nucleus accumbens. J Pharm Pharmacol 25:1003–1012Google Scholar
  18. Pycock CJ, Cater CM, Kerwin RW (1980) Effect of 6-hydroxydopamine lesions in the medial prefrontal cortex on neuortransmitter systems in subcortical sites in the rat. J Neurochem 34:91–102Google Scholar
  19. Shippenberg TS, Herz A (1988) Motivational effects of opioids: influence ofd-1 versusd-2 receptor antagonist. Eur J Pharmacol 151:233–241Google Scholar
  20. Spanagel R, Herz A, Shippenberg TS (1990) The effects of opioid peptides on dopamine release in the nucleus accumbens: an in vivo microdialysis study. J Neurochem 55:1734–1740Google Scholar
  21. Spyraki C, Fibinger HC, Phillips AG (1983) Attenuation of heroin reward in rats by disruption of the mesolimbic dopamine system. Psychopharmacology 79:278–283Google Scholar
  22. Stinus L, Koob GF, Ling N, Bloom FE, Le Moal M (1980) Locomotor activation induced by infusion of endorphins into the ventral tegmental area: evidence for opiate-dopamine interactions. Proc Natl Acad Sci USA 77:2323–2373Google Scholar
  23. Taghzouti K, Simon H, Louilot A, Herman JP, Le Moal JM (1985) Behavioral study after local injection of 6-hydroxydopamine into the nucleus accumbens in the rat. Brain Res 344:9–20Google Scholar
  24. Van Ree JM, Smyth DG, Colpaert FC (1979) Dependence creating properties of lipotropin c-fragment (β-endorphin): evidence for its internal control of behaviour. Life Sci 24:495–501Google Scholar
  25. Wise RA (1983) Brain neuronal systems mediating reward processes. In: Smith JE, Lane JD (eds) The neurobiologiy of opiate reward processes. Elsevier Biomedical Press, Amsterdam, pp 405–428Google Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Rainer Spanagel
    • 1
  • Albert Herz
    • 1
  • Regine Bals-Kubik
    • 1
  • Toni S. Shippenberg
    • 1
  1. 1.Department of NeuropharmacologyMax-Planck-Institut für PsychiatrieMartinsriedFederal Republic of Germany

Personalised recommendations