Differential prevention of morphine amnesia by antisense oligodeoxynucleotides directed against various Gi-protein alpha subunits.
The effect of the i.c.v. administration of pertussis toxin (PTX) and antisense oligodeoxynucleotide directed against the alpha subunit of different Gi-proteins (anti-Gialpha1, anti-Gialpha2, anti-Gialpha3) on amnesia induced by morphine was evaluated in the mouse passive avoidance test. The administration of morphine (6 - 10 mg kg(-1) i.p.) immediately after the training session produced amnesia that was prevented by PTX (0.25 microg per mouse i.c.v.) administered 7 days before the passive avoidance test. Anti-Gialpha1 (6.25 microg per mouse i.c.v.) and anti-Gialpha3 (12.5 microg per mouse i.c.v.), administered 18 and 24 h before the training session, prevented the morphine amnesia. By contrast, pretreatment with anti-Gialpha2 (3.12 - 25 microg per mouse i.c.v.) never modified the impairment of memory processes induced by morphine. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous motility and inspection activity, as revealed by the hole board test. These results suggest the important role played by Gi1 and Gi3 protein subtypes in the transduction mechanism involved in the impairment of memory processes produced by morphine.
Galeotti
N
N
Department of Preclinical and Clinical Pharmacology, Viale G. Pieraccini 6, I-50139 Florence, Italy.
Ghelardini
C
C
Bartolini
A
A
D000647:Amnesia / Q000139:chemically induced / Q000517:prevention & control* / Q000523:psychology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000037:antagonists & inhibitors; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009020:Morphine; D009294:Narcotics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000494:pharmacology*; D037342:Pertussis Toxin; D004856:Postural Balance / Q000187:drug effects; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D009294:Narcotics; D016376:Oligonucleotides, Antisense; D011518:Proto-Oncogene Proteins; D010566:Virulence Factors, Bordetella; D009020:Morphine; D037342:Pertussis Toxin; D051960:GTP-Binding Protein alpha Subunit, Gi2; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; C498016:Gnai2 protein, mouse; C417708:Gnai3 protein, mouse; D020962:Heterotrimeric GTP-Binding Proteins