The role of delta-opioid receptors in the discriminative stimulus properties of a low dose of methamphetamine.
The effects of selective mu-, delta- and kappa-opioid receptor agonists and antagonists on the discriminative stimulus properties of methamphetamine were examined in rats that had been trained to discriminate between methamphetamine (0.4 mg/kg) and saline. Methamphetamine produced a dose-related increase in methamphetamine-appropriate responses in all of the rats. In generalization tests, neither morphine (a mu-opioid receptor agonist: 0.3-10 mg/kg) nor 3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexo]benzeneacetamide (U50,488H: a kappa-opioid receptor agonist: 1.0-8.0 mg/kg) generalized to the discriminative stimulus properties of methamphetamine. A newly synthesized non-peptide selective delta-opioid receptor agonist 2-methyl-4aalpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12aalpha- octahydroquinolino(2,3,3,-g)isoquinoline (TAN-67: 32 mg/kg) partially generalized (70% methamphetamine-appropriate responses) to the discriminative stimulus properties of methamphetamine. In combination tests, pretreatment with the mu- and kappa-opioid receptor antagonists, beta-funaltrexamine (9.0 mg/kg) and nor-binaltorphimine (10 mg/kg), respectively, had little or no influence on the discriminative stimulus properties of methamphetamine. In contrast, pretreatment with naltrindole (a non-selective delta-opioid receptor antagonist: 3.0 mg/kg) or naltriben (a selective delta2-opioid receptor antagonist: 1.0 mg/kg), but not with 7-benzylidenenaltrexone (a selective delta1-opioid receptor antagonist: 0.5 and 1.0 mg/kg), significantly attenuated the discriminative stimulus properties of methamphetamine. However, naltrindole (3.0 mg/kg) did not significantly attenuate the discriminative stimulus properties of methamphetamine at a higher training dose (1.0 mg/kg). Our findings may have some bearing on the relative importance of the role of delta-opioid (especially delta2-opioid) receptors in the discriminative stimulus properties of a low dose of methamphetamine.
Suzuki
T
T
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan. suzuki@hoshi.ac.jp
Mori
T
T
Tsuji
M
M
Misawa
M
M
Nagase
H
H
D000818:Animals; D001597:Benzylidene Compounds / Q000008:administration & dosage; D000697:Central Nervous System Stimulants / Q000008:administration & dosage*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology*
D001597:Benzylidene Compounds; D000697:Central Nervous System Stimulants; D011804:Quinolines; D017465:Receptors, Opioid, delta; C094142:TAN 67; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; C051844:norbinaltorphimine; D008694:Methamphetamine; D009271:Naltrexone; C055382:naltrindole