Premium
The Discriminative Stimulus Effects of the Neurotensin NTS 1 Receptor Agonist PD 149163 in Rats: Stimulus Generalization Testing with Dopamine D 1 and D 2 Receptor Ligands
Author(s) -
Prus Adam J.,
Schuck Candice J.,
Rusch Kristoffer R.,
Carey Lawrence M.
Publication year - 2014
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.21171
Subject(s) - quinpirole , agonist , raclopride , dopamine receptor d2 , sch 23390 , pharmacology , dopamine receptor d3 , chemistry , receptor , apomorphine , dopamine receptor , dopamine , medicine , endocrinology , psychology , neuroscience , biology
Preclinical ResearchBrain‐penetrant neurotensin NTS 1 receptor agonists produce antipsychotic drug‐like effects in animal models, including inhibition of conditioned avoidance responding and reversal of psychostimulant‐induced hyperactivity and stereotypy. Allosteric interactions between NTS 1 receptors and dopamine D 2 receptors may account for some of these antipsychotic effects. In order to determine the role that dopamine receptors may play in the behavioral effects produced by activation of NTS 1 receptors, a drug discrimination approach was used in rats to evaluate the potential mediation of NTS 1 receptor agonist stimulus effects by dopamine D 1 and D 2 receptors. Rats were trained to discriminate either the NTS 1 receptor agonist PD 149163, the D 1 receptor agonist SKF 81297, or the D 2 receptor agonist quinpirole from vehicle in a two choice drug discrimination task. Full stimulus generalization occurred from PD 149163 to the typical antipsychotic drug and D 2 receptor‐preferring antagonist haloperidol. However, stimulus generalization did not occur from SKF 81297 or quinpirole to PD 149163. The discriminative cue for SKF 91297 and quinpirole was fully blocked the D 1 receptor antagonist SCH 23390 and the D 2/3 receptor antagonist raclopride, respectively. Cross generalization did not occur between SKF 91297 and quinpirole. Based on these findings, the stimulus effects of PD 149163 may be mediated, in part, through D 2 receptor antagonism, but this may only be evident when PD 149163 is used as the training drug.