Facilitation of brain stimulation reward by MK-801 (dizocilpine) may be independent of D2-like dopamine receptor stimulation in rats.

Abstract:

RATIONALE:Dopamine (DA) and glutamate (Glu) interactions in the mesocorticolimbic pathway may regulate motivation and reward and contribute to schizophrenia and drug abuse. We have recently demonstrated synergistic effects of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor blockade and D(2/3) DA receptor stimulation in brain stimulation reward (BSR). OBJECTIVES:This study was conducted to explore interactions between DA and Glu systems in BSR using the NMDA receptor antagonist MK-801 and the DA receptor agonists 7-OH-DPAT and apomorphine. METHODS:Systemic effects of these compounds were measured in male Sprague-Dawley rats using rate-frequency threshold analysis of ventral tegmental area (VTA) BSR (n=27). Effects of bilateral applications of MK-801 and 7-OH-DPAT into the nucleus accumbens (NAS) shell subregion were also investigated (n=10). RESULTS:MK-801 (0.03 or 0.13 mg kg(-1) i.p. or 0.66 mug intra-NAS) reduced reward thresholds while 7-OH-DPAT (0.03 mg kg(-1) s.c. or 5.0 microg intra-NAS) or apomorphine (0.05 mg kg(-1), s.c.) increased this measure. MK-801 combined with apomorphine or with 7-OH-DPAT, systemically or in the NAS shell, induced additive effects. CONCLUSIONS:Lack of interaction between DA agonists and MK-801 in this study contrasts with our previous work showing synergistic reward-decreased effects of AMPA/kainate receptor blockade and D(2/3) DA receptor stimulation in the NAS shell, and indicates possible independence of DA and N-methyl-D-aspartate (NMDA) receptor effects in VTA electrical self-stimulation.

journal_title

Psychopharmacology

authors

Clements RL,Greenshaw AJ

doi

10.1007/s00213-005-0039-y

subject

Has Abstract

pub_date

2005-10-01 00:00:00

pages

65-74

issue

1

eissn

0033-3158

issn

1432-2072

journal_volume

182

pub_type

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