Functional neuroanatomy of the ventral striopallidal GABA pathway. New sites of intervention in the treatment of schizophrenia

J Neurosci Methods. 2001 Aug 15;109(1):31-9. doi: 10.1016/s0165-0270(01)00398-3.

Abstract

Microdialysis was employed to investigate the dopamine, cholecystokinin (CCK) and neurotensin receptor regulation of ventral striopallidal GABA transmission by intra-accumbens perfusion with selective receptor ligands and monitoring local or ipsilateral ventral pallidal GABA release. In the dual probe studies intra-accumbens perfusion with the dopamine D1 and D2 receptor agonists SKF28293 and pergolide had no effect on ventral pallidal GABA, while both the D1 and D2 receptor antagonists SCH23390 and raclopride increased ventral pallidal GABA release. In contrast, intra-accumbens CCK decreased ventral pallidal GABA release and this was reversed by local perfusion with the CCK2 receptor antagonist PD134308 but not the CCK1 receptor antagonist L-364,718. In a single probe study intra-accumbens neurotensin increased local GABA release, which was strongly potentiated when the peptidase inhibitor phosphodiepryl 08 was perfused together with neurotensin. In addition, the neurotensin receptor antagonist SR48692 counteracted this phosphodiepryl 08 induced potentiated increased in GABA release. Taken together, these findings indicate that mesolimbic dopamine and CCK exert a respective tonic and phasic inhibition of ventral pallidal GABA release while the antipsychotic activity associated with D1 and D2 receptor antagonists may be explained by their ability to increase ventral striopallidal GABA transmission. Furthermore, the findings suggest that CCK2 receptor antagonists and neurotensin endopeptidase inhibitors may be useful antipsychotics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cholecystokinin / agonists
  • Cholecystokinin / antagonists & inhibitors
  • Dopamine / metabolism
  • Dopamine D2 Receptor Antagonists
  • Extracellular Space / metabolism
  • Globus Pallidus / cytology
  • Globus Pallidus / drug effects
  • Globus Pallidus / metabolism*
  • Male
  • Microdialysis / methods*
  • Neural Inhibition / drug effects
  • Neural Inhibition / physiology*
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotensin / agonists
  • Neurotensin / antagonists & inhibitors
  • Nucleus Accumbens / cytology
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin / agonists
  • Receptors, Cholecystokinin / antagonists & inhibitors
  • Receptors, Cholecystokinin / metabolism
  • Receptors, Dopamine D1 / agonists
  • Receptors, Dopamine D1 / antagonists & inhibitors
  • Receptors, Dopamine D1 / metabolism
  • Receptors, Dopamine D2 / agonists
  • Receptors, Dopamine D2 / metabolism
  • Receptors, Neurotensin / agonists
  • Receptors, Neurotensin / antagonists & inhibitors
  • Schizophrenia / metabolism
  • Schizophrenia / pathology
  • Schizophrenia / physiopathology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology
  • gamma-Aminobutyric Acid / metabolism*

Substances

  • Dopamine D2 Receptor Antagonists
  • Receptor, Cholecystokinin B
  • Receptors, Cholecystokinin
  • Receptors, Dopamine D1
  • Receptors, Dopamine D2
  • Receptors, Neurotensin
  • Neurotensin
  • gamma-Aminobutyric Acid
  • Cholecystokinin
  • Dopamine