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Dopamine D2‐like receptors mediate the discriminative stimulus effects of delta‐9‐tetrahydrocannabinol (delta‐9‐THC) in rhesus monkeys
Author(s) -
Stewart Jennifer L,
McMahon Lance R.
Publication year - 2010
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.24.1_supplement.581.8
Subject(s) - pharmacology , dopamine , agonist , quinpirole , chemistry , dopamine receptor d2 , delta 9 tetrahydrocannabinol , amphetamine , monoaminergic , dopamine receptor , medicine , receptor , endocrinology , serotonin , cannabinoid
Monoamines are implicated in the behavioral effects of CB 1 receptor agonists; dopamine, in particular, could mediate the abuse liability of marijuana. The objective of this study was to investigate the capacity of monoaminergic ligands to modify the discriminative stimulus effects of Δ 9 ‐THC (0.1 mg/kg i.v.) in rhesus monkeys. The Δ 9 ‐THC discriminative stimulus was attenuated by cocaine (0.32–1.78 mg/kg) and amphetamine (0.1–0.56 mg/kg), while acute administration of the norepinephrine and serotonin transporter inhibitors desipramine (10–17.8 mg/kg) and imipramine (10–17.8 mg/kg) did not modify Δ 9 ‐THC. The involvement of dopamine receptor subtypes was then investigated; the dopamine D 1 ‐like receptor agonists (±)‐SKF 38393 (3.2–10 mg/kg) and (±)‐6‐Chloro‐PB (0.56–5.6 mg/kg) did not modify the Δ 9 ‐THC discriminative stimulus. The dopamine D 2 ‐like receptor antagonist haloperidol (0.0032–0.01 mg/kg) and the dopamine D 2 ‐like receptor agonist quinpirole significantly enhanced the discriminative stimulus effects of Δ 9 ‐THC. Drugs that directly or indirectly interact with dopamine D 2 ‐like receptors play an important role in mediating the behavioral effects of cannabinoids; the mechanism responsible for attenuation of Δ 9 ‐THC by cocaine and amphetamine remains unclear. Supported by USPHS grant DA 19222 and DA 26781.