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Effects of Acute Administration of Sigma Receptor Ligands on Mesolimbic Dopamine Neurotransmission in Rats
Author(s) -
Tanda Gianluigi,
GarcésRamírez Linda,
Green Jennifer L,
Hiranita Takato,
Katz Jonathan L
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.745.4
Subject(s) - nucleus accumbens , microdialysis , agonist , dopamine , chemistry , pharmacology , neurotransmission , antagonist , neurotransmitter , receptor , medicine , endocrinology , biochemistry
Sigma receptors (σRs) can modulate cocaine's behavioral effects, which are related to increased mesolimbic dopamine (DA) neurotransmission, and σR agonists can maintain responding in rats that self administer cocaine. We report here effects of σR ligands on DA transmission in rats implanted with vertical microdialysis probes in the nucleus accumbens shell. Cocaine (0.1‐1.0 mg/kg iv) or a non‐selective σ 1/2 agonist (DTG: 1.0‐5.6 mg/kg iv) dose‐dependently increased DA levels to 275 and 150% of baseline, respectively. In contrast, the preferential σ 1 R agonist, PRE‐084 (0.32‐3.2 mg/kg iv), did not significantly modify DA levels. The preferential σ 1 R antagonist, BD 1063 (10‐30 mg/kg ip), administered alone transiently (<30 min) and dose‐dependently increased DA levels to a maximum of 150%, and later decreased DA levels to ~80% of baseline. The σ 1/2 antagonist, BD 1008 (10 mg/kg ip) modestly decreased DA levels over the 2 hr following its administration. The effects of 5.6 mg/kg DTG were attenuated by BD 1008 (10 mg/kg ip), but not by BD 1063 (10‐30 mg/kg ip). In sum, the results show that acute administration of σR ligands can increase DA transmission in a brain area involved in the reinforcing effects of cocaine, and this effect appears to be mediated by the σ 2 R. Studies are in progress to understand if σR ligands can also modulate cocaine‐induced stimulation of DA transmission.