Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys

substitution during phencyclidine self-administration and withdrawal

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8 Citations (Scopus)

Abstract

Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (±) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (±)-NANM were reistated in subsequent replications of the experiment. During PCP withdrawal food-maintained responding was substantially disrupted, especially during the first two days. Reinstatement of PCP or (+)-NANM resulted in a rapid recovery of food maintained behavior, and the number of (+)-NANM deliveries was comparable to the baseline PCP deliveries. Food- and drug-maintained responding did not reliably recover when (-)- or (±)-NANM was introduced after four days of water substitution. However, after 5 days when (-)- or (±)-NANM was replaced by PCP, food and liquid-maintained responding immediately returned to baseline rates. These results agree with previous findings from intravenous self-administration studies that only the dextro (+)-isomer of NANM functions as a reinforcer. Neither taste factors nor PCP withdrawal altered these reinforcing effects.

Original languageEnglish (US)
Pages (from-to)493-500
Number of pages8
JournalPharmacology, Biochemistry and Behavior
Volume30
Issue number2
DOIs
StatePublished - Jan 1 1988

Fingerprint

Phencyclidine
Stereoisomerism
Self Administration
Macaca mulatta
Oral Administration
Substitution reactions
Water
Isomers
Food
Appointments and Schedules
Haplorhini
SK&F 10047
Liquids
Pharmaceutical Preparations
Aptitude
Solenoids
Lip
Intravenous Administration
Contacts (fluid mechanics)
Drinking

Keywords

  • Behavioral dependence
  • N-Allylnormetazocine
  • NANM
  • Oral route
  • PCP
  • Phencyclidine
  • Rhesus monkeys
  • Self-administration
  • SKF-10,047
  • Stereoisomers

Cite this

@article{ce965e0f4e2b41d7831dad254af748e1,
title = "Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys: substitution during phencyclidine self-administration and withdrawal",
abstract = "Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (±) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (±)-NANM were reistated in subsequent replications of the experiment. During PCP withdrawal food-maintained responding was substantially disrupted, especially during the first two days. Reinstatement of PCP or (+)-NANM resulted in a rapid recovery of food maintained behavior, and the number of (+)-NANM deliveries was comparable to the baseline PCP deliveries. Food- and drug-maintained responding did not reliably recover when (-)- or (±)-NANM was introduced after four days of water substitution. However, after 5 days when (-)- or (±)-NANM was replaced by PCP, food and liquid-maintained responding immediately returned to baseline rates. These results agree with previous findings from intravenous self-administration studies that only the dextro (+)-isomer of NANM functions as a reinforcer. Neither taste factors nor PCP withdrawal altered these reinforcing effects.",
keywords = "Behavioral dependence, N-Allylnormetazocine, NANM, Oral route, PCP, Phencyclidine, Rhesus monkeys, Self-administration, SKF-10,047, Stereoisomers",
author = "Carroll, {Marilyn E}",
year = "1988",
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day = "1",
doi = "10.1016/0091-3057(88)90486-8",
language = "English (US)",
volume = "30",
pages = "493--500",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
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TY - JOUR

T1 - Oral self-administration of N-allylnormetazocine (SKF-10,047) stereoisomers in rhesus monkeys

T2 - substitution during phencyclidine self-administration and withdrawal

AU - Carroll, Marilyn E

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (±) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (±)-NANM were reistated in subsequent replications of the experiment. During PCP withdrawal food-maintained responding was substantially disrupted, especially during the first two days. Reinstatement of PCP or (+)-NANM resulted in a rapid recovery of food maintained behavior, and the number of (+)-NANM deliveries was comparable to the baseline PCP deliveries. Food- and drug-maintained responding did not reliably recover when (-)- or (±)-NANM was introduced after four days of water substitution. However, after 5 days when (-)- or (±)-NANM was replaced by PCP, food and liquid-maintained responding immediately returned to baseline rates. These results agree with previous findings from intravenous self-administration studies that only the dextro (+)-isomer of NANM functions as a reinforcer. Neither taste factors nor PCP withdrawal altered these reinforcing effects.

AB - Orally-delivered N-allylnormetazocine (NANM) and its isomers were tested for their ability to function as reinforcers by substituting them for phencyclidine (PCP). Two monkeys were trained to self-administer PCP (0.25 mg/ml) and water under concurrent fixed-ratio (FR) 16 schedules during 3-hr sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking devices. When the dextro (+)-isomer of NANM (0.062-1 mg/ml) was substituted for PCP, response rates increased and then decreased in an inverted U-shaped concentration-response function with peak response rates comparable to those maintained by PCP. Drug intake ranged from 2.8 to 25.7 mg/kg across the two monkeys and five concentrations. Water-maintained responding was considerably lower than drug-maintained behavior indicating that NANM was functioning as a reinforcer. As previously reported for PCP, almost all of the (+)-NANM was self-administered during the first half of the session. Substitution of the levo (-)-isomer of NANM resulted in an immediate decline to low response rates that were not distinguishable from those maintained by water. The racemic form (±) of NANM was also not self-administered in excess of concurrent water. In the second experiment concurrent PCP- and water-maintained responding were reestablished under FR 8 schedules during three 6.5-hr sessions daily. Food (6 g/pellet) was available under FR 64 and FR 80 schedules during three 1-hr sessions immediately preceding the liquid components. Water was then substituted for PCP for four days and PCP, (+)-, (-)- or (±)-NANM were reistated in subsequent replications of the experiment. During PCP withdrawal food-maintained responding was substantially disrupted, especially during the first two days. Reinstatement of PCP or (+)-NANM resulted in a rapid recovery of food maintained behavior, and the number of (+)-NANM deliveries was comparable to the baseline PCP deliveries. Food- and drug-maintained responding did not reliably recover when (-)- or (±)-NANM was introduced after four days of water substitution. However, after 5 days when (-)- or (±)-NANM was replaced by PCP, food and liquid-maintained responding immediately returned to baseline rates. These results agree with previous findings from intravenous self-administration studies that only the dextro (+)-isomer of NANM functions as a reinforcer. Neither taste factors nor PCP withdrawal altered these reinforcing effects.

KW - Behavioral dependence

KW - N-Allylnormetazocine

KW - NANM

KW - Oral route

KW - PCP

KW - Phencyclidine

KW - Rhesus monkeys

KW - Self-administration

KW - SKF-10,047

KW - Stereoisomers

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U2 - 10.1016/0091-3057(88)90486-8

DO - 10.1016/0091-3057(88)90486-8

M3 - Article

VL - 30

SP - 493

EP - 500

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

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ER -