Comparison of the discriminative stimulus effects of SKF 38393 with those of other dopamine receptor agonists

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Comparison of the discriminative stimulus effects of SKF 38393 with those of other dopamine receptor agonists. / Desai, RI; Terry, Philip; Katz, JL.

In: Behavioural Pharmacology, Vol. 14, 01.01.2003, p. 223-228.

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@article{d9ff74971be84675bb600a43ba169c6b,
title = "Comparison of the discriminative stimulus effects of SKF 38393 with those of other dopamine receptor agonists",
abstract = "The dopamine D(1)-like receptor agonists have traditionally been defined molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence correlating the effectiveness of these drugs in behavioral assays and their effectiveness biochemically has not been forthcoming. The present study compared the discriminative-stimulus effects of the D(1)-like partial agonist SKF 38393 with several other D(1)-like agonists, an indirect agonist, cocaine, and a D(2)-like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule, 30 consecutive responses on one of two keys were reinforced with food presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30 consecutive responses on the alternative key were reinforced after saline injection. When daily performances were stable, substitution patterns for several compounds were assessed during test sessions in which 30 consecutive responses on either key were reinforced. Quinpirole and cocaine each produced saline-appropriate responding. In contrast, the D(1)-like agonists, SKF 75670 and SKF 77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered a full agonist based on adenylyl cyclase assays, was less effective in substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the partial agonist SKF 75670. The present results suggest that second messenger effects other than stimulation of adenylyl cyclase may play an important role in the behavioral effects of dopamine D(1)-like agonists.",
keywords = "drug discrimination, cocaine, SKIF 38393, dopamine D1 receptors, quinpirole, adenylyl cyclase, rat",
author = "RI Desai and Philip Terry and JL Katz",
year = "2003",
month = jan,
day = "1",
doi = "10.1097/01.fbp.0000073701.15098.fa",
language = "English",
volume = "14",
pages = "223--228",
journal = "Behavioural Pharmacology",
issn = "0955-8810",
publisher = "Lippincott Williams and Wilkins",

}

RIS

TY - JOUR

T1 - Comparison of the discriminative stimulus effects of SKF 38393 with those of other dopamine receptor agonists

AU - Desai, RI

AU - Terry, Philip

AU - Katz, JL

PY - 2003/1/1

Y1 - 2003/1/1

N2 - The dopamine D(1)-like receptor agonists have traditionally been defined molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence correlating the effectiveness of these drugs in behavioral assays and their effectiveness biochemically has not been forthcoming. The present study compared the discriminative-stimulus effects of the D(1)-like partial agonist SKF 38393 with several other D(1)-like agonists, an indirect agonist, cocaine, and a D(2)-like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule, 30 consecutive responses on one of two keys were reinforced with food presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30 consecutive responses on the alternative key were reinforced after saline injection. When daily performances were stable, substitution patterns for several compounds were assessed during test sessions in which 30 consecutive responses on either key were reinforced. Quinpirole and cocaine each produced saline-appropriate responding. In contrast, the D(1)-like agonists, SKF 75670 and SKF 77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered a full agonist based on adenylyl cyclase assays, was less effective in substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the partial agonist SKF 75670. The present results suggest that second messenger effects other than stimulation of adenylyl cyclase may play an important role in the behavioral effects of dopamine D(1)-like agonists.

AB - The dopamine D(1)-like receptor agonists have traditionally been defined molecularly by their efficacy in stimulating adenylyl cyclase. However, evidence correlating the effectiveness of these drugs in behavioral assays and their effectiveness biochemically has not been forthcoming. The present study compared the discriminative-stimulus effects of the D(1)-like partial agonist SKF 38393 with several other D(1)-like agonists, an indirect agonist, cocaine, and a D(2)-like agonist, quinpirole. Rats were trained under a fixed-ratio 30-response schedule to discriminate SKF 38393 (5.6 mg/kg) from vehicle. Under this schedule, 30 consecutive responses on one of two keys were reinforced with food presentation after a pre-session injection of 5.6 mg/kg SKF 38393, and 30 consecutive responses on the alternative key were reinforced after saline injection. When daily performances were stable, substitution patterns for several compounds were assessed during test sessions in which 30 consecutive responses on either key were reinforced. Quinpirole and cocaine each produced saline-appropriate responding. In contrast, the D(1)-like agonists, SKF 75670 and SKF 77434, fully substituted for SKF 38393. Curiously, SKF 82958, which is considered a full agonist based on adenylyl cyclase assays, was less effective in substituting for SKF 38393 (maximum drug-appropriate responding 66%) than was the partial agonist SKF 75670. The present results suggest that second messenger effects other than stimulation of adenylyl cyclase may play an important role in the behavioral effects of dopamine D(1)-like agonists.

KW - drug discrimination

KW - cocaine

KW - SKIF 38393

KW - dopamine D1 receptors

KW - quinpirole

KW - adenylyl cyclase

KW - rat

UR - http://www.scopus.com/inward/record.url?scp=0038348598&partnerID=8YFLogxK

U2 - 10.1097/01.fbp.0000073701.15098.fa

DO - 10.1097/01.fbp.0000073701.15098.fa

M3 - Article

C2 - 12799524

VL - 14

SP - 223

EP - 228

JO - Behavioural Pharmacology

JF - Behavioural Pharmacology

SN - 0955-8810

ER -