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Titolo:
EFFECTS OF N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS ON DISCRIMINATIVE STIMULUS EFFECTS OF NALOXONE IN MORPHINE-DEPENDENT RATS USING THE Y-MAZE DRUG DISCRIMINATION PARADIGM
Autore:
MEDVEDEV IO; DRAVOLINA OA; BESPALOV AY;
Indirizzi:
PAVLOV MED UNIV,INST PHARMACOL,LAB BEHAV PHARMACOL,6-8 LEV TOLSTOY STST PETERSBURG 197089 RUSSIA PAVLOV MED UNIV,INST PHARMACOL,LAB BEHAV PHARMACOL ST PETERSBURG 197089 RUSSIA
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 286, anno: 1998,
pagine: 1260 - 1268
SICI:
0022-3565(1998)286:3<1260:EONRAO>2.0.ZU;2-Q
Fonte:
ISI
Lingua:
ENG
Soggetto:
PRECIPITATED OPIOID WITHDRAWAL; COMPETITIVE NMDA ANTAGONIST; GLUTAMATE ANTAGONISTS; PHENCYCLIDINE-LIKE; OPIATE WITHDRAWAL; RHESUS-MONKEYS; LOCUS-CERULEUS; MK-801; SALINE; PHARMACOLOGY;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
40
Recensione:
Indirizzi per estratti:
Citazione:
I.O. Medvedev et al., "EFFECTS OF N-METHYL-D-ASPARTATE RECEPTOR ANTAGONISTS ON DISCRIMINATIVE STIMULUS EFFECTS OF NALOXONE IN MORPHINE-DEPENDENT RATS USING THE Y-MAZE DRUG DISCRIMINATION PARADIGM", The Journal of pharmacology and experimental therapeutics, 286(3), 1998, pp. 1260-1268

Abstract

The present study assessed the ability of various site-selective N-methyl-D-aspartate (NMDA) receptor antagonists to affect the discriminative stimulus properties of naloxone in morphine-dependent rats. Adult male Wistar rats were trained to discriminate 0.1 mg/kg of s.c. naloxone from saline using a Y-maze shock-avoidance procedure. Naloxone-appropriate responding was exhibited as a function of naloxone dose (0.01-1.0 mg/kg, ED50 = 0.03 mg/kg) and was also observed when morphine treatment temporarily was discontinued (8-96 hr, peak at 24 hr). Discriminative stimulus effects of naloxone (0.1-3.0 mg/kg) were antagonized bymorphine (10-100 mg/kg). Ligands of peripheral opioid receptors failed to either substitute for naloxone (methylnaloxone, 0.1-3.0 mg/kg) orattenuate naloxone's stimulus effects (loperamide, 1-30 mg/kg). In rats treated with the training dose of naloxone, administration of dizocilpine (0.03-0.3 mg/kg) and D-CPPene (1-10 mg/kg) decreased levels of naloxone-appropriate responding, whereas memantine (1-30 mg/kg), ACEA-1021 (10 and 50 mg/kg) and eliprodil (3-30 mg/kg) seemed to have little or no effects. Meanwhile, all NMDA receptor antagonists produced a decrease in the occurrence of two or more of the following opioid withdrawal signs: weight loss, forelimb tremor, ptosis, diarrhea and ''wet-dog''-like shaking. Additionally, dizocilpine (0.1 mg/kg), D-CPPene (5.6 mg/kg) and ACEA-1021 (50 mg/kg) but not memantine (10 mg/kg) or eliprodil (30 mg/kg) significantly reduced the naloxone-appropriate escape area selection when administered during the period of suspended morphine treatment 24 hr after the last morphine injection. Thus, NMDA receptor antagonists appear to inhibit the discriminative stimulus effects of both naloxone-precipitated and spontaneous morphine withdrawal, and this ability depends on the type of antagonist applied.

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Documento generato il 28/11/20 alle ore 04:44:17