The reinforcing and discriminative stimulus effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane in rhesus monkeys

Michael A. Nader, Kathleen (Kathy) Grant, Huw M L Davies, Robert H. Mach, Steven R. Childers

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

2β-propanoyl-3β-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits dopamine uptake, binding with high affinity and selectivity to the dopamine transporter. In the present study, the behavioral effects of PTT were evaluated in two models of cocaine abuse: drug self-administration and drug discrimination. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Presession administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self- administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to 1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were evaluated in a separate group of monkeys (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the discriminative stimulus effects of PTT (0.0030.1 mg/kg, i.m.) were evaluated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-acting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique behavioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to cocaine.

Original languageEnglish (US)
Pages (from-to)541-550
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume280
Issue number2
StatePublished - 1997
Externally publishedYes

Fingerprint

Macaca mulatta
Cocaine
Injections
Self Administration
2-propanoyl-3-(4-tolyl)tropane
Haplorhini
Appointments and Schedules
Cocaine-Related Disorders
Dopamine Plasma Membrane Transport Proteins
Dopamine Agonists
Pharmaceutical Preparations
Dopamine

ASJC Scopus subject areas

  • Pharmacology

Cite this

The reinforcing and discriminative stimulus effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane in rhesus monkeys. / Nader, Michael A.; Grant, Kathleen (Kathy); Davies, Huw M L; Mach, Robert H.; Childers, Steven R.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 280, No. 2, 1997, p. 541-550.

Research output: Contribution to journalArticle

@article{74b5067c019f483dbbe334d820f63498,
title = "The reinforcing and discriminative stimulus effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane in rhesus monkeys",
abstract = "2β-propanoyl-3β-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits dopamine uptake, binding with high affinity and selectivity to the dopamine transporter. In the present study, the behavioral effects of PTT were evaluated in two models of cocaine abuse: drug self-administration and drug discrimination. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Presession administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self- administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to 1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were evaluated in a separate group of monkeys (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the discriminative stimulus effects of PTT (0.0030.1 mg/kg, i.m.) were evaluated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-acting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique behavioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to cocaine.",
author = "Nader, {Michael A.} and Grant, {Kathleen (Kathy)} and Davies, {Huw M L} and Mach, {Robert H.} and Childers, {Steven R.}",
year = "1997",
language = "English (US)",
volume = "280",
pages = "541--550",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - The reinforcing and discriminative stimulus effects of the novel cocaine analog 2β-propanoyl-3β-(4-tolyl)-tropane in rhesus monkeys

AU - Nader, Michael A.

AU - Grant, Kathleen (Kathy)

AU - Davies, Huw M L

AU - Mach, Robert H.

AU - Childers, Steven R.

PY - 1997

Y1 - 1997

N2 - 2β-propanoyl-3β-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits dopamine uptake, binding with high affinity and selectivity to the dopamine transporter. In the present study, the behavioral effects of PTT were evaluated in two models of cocaine abuse: drug self-administration and drug discrimination. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Presession administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self- administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to 1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were evaluated in a separate group of monkeys (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the discriminative stimulus effects of PTT (0.0030.1 mg/kg, i.m.) were evaluated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-acting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique behavioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to cocaine.

AB - 2β-propanoyl-3β-(4-tolyl)-tropane (PTT), is a cocaine analog that inhibits dopamine uptake, binding with high affinity and selectivity to the dopamine transporter. In the present study, the behavioral effects of PTT were evaluated in two models of cocaine abuse: drug self-administration and drug discrimination. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (0.03 and 0.1 mg/kg/injection, i.v.) under a fixed-interval 5-min schedule. Presession administration of PTT (0.03-0.3 mg/kg, i.v.) or cocaine (0.3-3.0 mg/kg, i.v.) were evaluated. At both self- administered doses of cocaine, PTT decreased response rates and total session intakes and was approximately 0.5 to 1.0 log units more potent than cocaine. In experiment 2, the reinforcing effects of PTT (0.003-0.1 mg/kg/injection) were evaluated in a separate group of monkeys (n = 4) responding under a fixed-interval 5-min schedule of cocaine (0.03 mg/kg/injection) presentation. When substituted for cocaine, PTT maintained response rates similar to saline-maintained rates and significantly lower than rates maintained by cocaine (0.003-0.3 mg/kg/injection). Total session PTT intake was significantly lower than cocaine intake. In experiment 3, the discriminative stimulus effects of PTT (0.0030.1 mg/kg, i.m.) were evaluated in monkeys (n = 3) trained to discriminate cocaine (0.2 mg/kg, i.m.) from saline (0.5 ml). PTT substituted for cocaine in a dose-dependent manner and was 0.5 to 1.0 log units more potent than cocaine. At the highest PTT dose, cocaine-appropriate responding was observed 8 to 24 hr after the injection. These results demonstrated that the long-acting indirect dopamine agonist PTT was effective in decreasing cocaine self-administration and in abuse liability testing showed a unique behavioral profile, not functioning as a reinforcer when substituted for cocaine and producing discriminative stimulus effects similar to cocaine.

UR - http://www.scopus.com/inward/record.url?scp=0030899415&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030899415&partnerID=8YFLogxK

M3 - Article

C2 - 9023262

AN - SCOPUS:0030899415

VL - 280

SP - 541

EP - 550

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -