Nucleus accumbens serotonin1A receptors control cocaine-induced hyperactivity but not local serotonin increase: an in vivo microdialysis study

Neuropharmacology. 2004 Aug;47(2):205-15. doi: 10.1016/j.neuropharm.2004.03.020.

Abstract

The nucleus accumbens (Nac) is an important structure for cocaine-induced hyperactivity and receives a dense serotonergic (5-HT) innervation. Previous studies showed that a systemic activation of 5-HT(1A) receptors potentiates cocaine-induced hyperlocomotion, but attenuates the cocaine-induced 5-HT increase in the Nac. In order to address the role of Nac 5-HT(1A) receptors in the control of cocaine-induced and spontaneous behavioural activity and local 5-HT release, we used in vivo microdialysis in freely moving rats. The 5-HT(1A)-receptor agonist, 8-OH-DPAT (0, 1 and 10 microM), was applied locally into the Nac by reverse dialysis followed by a cocaine (10 mg/kg) or saline i.p. injection. The Nac 5-HT(1A)-receptor activation potentiated cocaine-induced hyperlocomotion, but attenuated rearing behaviour dose-dependently. Parallel to that, the cocaine-induced increase in Nac 5-HT dialysate level was unaffected, as were the decreases in 5-HIAA and DOPAC dialysate levels after cocaine. In saline treated rats, the local application of 8-OH-DPAT into the Nac affected neither spontaneous behavioural activity nor 5-HT, 5-HIAA or DOPAC dialysate levels in the Nac. These data suggest that Nac 5-HT(1A) receptors exert a bi-directional control of cocaine-induced hyperactivity, while not affecting spontaneous behaviour. Furthermore, accumbal 5-HT(1A) receptors do not appear to be directly involved in the acute effects of cocaine on 5-HT, 5-HIAA or DOPAC levels in the Nac.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / pharmacology*
  • Hydroxyindoleacetic Acid / metabolism
  • Hyperkinesis / chemically induced*
  • Hyperkinesis / psychology
  • Male
  • Microdialysis
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Nucleus Accumbens / physiology*
  • Rats
  • Rats, Wistar
  • Receptor, Serotonin, 5-HT1A / drug effects
  • Receptor, Serotonin, 5-HT1A / physiology*
  • Serotonin / metabolism*
  • Serotonin Receptor Agonists / pharmacology

Substances

  • Serotonin Receptor Agonists
  • 3,4-Dihydroxyphenylacetic Acid
  • Receptor, Serotonin, 5-HT1A
  • Serotonin
  • Hydroxyindoleacetic Acid
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Cocaine