Assessment of the discriminative stimulus effects of the D3 dopamine antagonist PNU-99194A in rats: comparison with psychomotor stimulants.
The present study examined the discriminative stimulus effects of the D3 dopamine receptor antagonist PNU-99194A [5,6-di-methoxy-2-(dipropylamino)indan-hydrochloride] in male Sprague-Dawley rats. Eight rats were trained to discriminate cocaine (10 mg/kg, i.p.) from saline in a two-choice, water-reinforced drug discrimination procedure. In tests of stimulus generalization, PNU-99194A (1.25-40.0 mg/kg, s.c. and i.p.) did not substitute for cocaine. PNU-99194A (5.0-20 mg/kg) also did not significantly block the discrimination of cocaine (10 mg/kg), nor did it potentiate a low dose (1.25 mg/kg) of cocaine. A separate group of eight rats were trained to discriminate PNU-99194A from saline. These subjects met the discrimination criterion within an average of 68 (S.E.M. = 6.5) training sessions; the ED50 for PNU-99194A was 2.6 mg/kg. In stimulus generalization tests, cocaine (1.25-10 mg/kg) did not substitute for PNU-99194A, when administered by either i.p. or by s.c. injection. In addition, neither amphetamine (0.25-1.0 mg/kg) nor caffeine (8.0-64 mg/kg) produced stimulus generalization in these rats. These results indicate that D3 receptors do not play a critical role in the discriminative stimulus effects of cocaine. Furthermore, although PNU-99194A is capable of establishing and maintaining discriminative stimulus control in rats, the effects of this D3-preferring antagonist are dissimilar from those of psychomotor stimulants. Given the unique behavioral profile of D3 receptor antagonists, the potential utility of these agents as adjunctive treatments for psychostimulant abuse is discussed.
Baker
L E
LE
Department of Psychology, Western Michigan University, Kalamazoo 49008, USA.
Miller
M E
ME
Svensson
K A
KA
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects; D004192:Discrimination, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007189:Indans / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050637:Receptors, Dopamine D3; D013268:Stimulation, Chemical
D000697:Central Nervous System Stimulants; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D007189:Indans; D050637:Receptors, Dopamine D3; C086335:(5,6-dimethoxyindan-2-yl)dipropylamine; D000661:Amphetamine; D003042:Cocaine