Role of 5-HT(1B) receptors in the sensitization to amphetamine in mice.
The present study was designed to determine how 5-HT(1B) receptor ligands affected the development or the expression phase of sensitization to the amphetamine-induced locomotor response in mice. Mice were treated repeatedly (for 5 days) with amphetamine (2.5 mg/kg) in combination with either vehicle, N-[3-[3-(dimethylamino)ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride (SB 216641; an antagonist of 5-HT(1B) receptors), 3-(1,2,5,6-tetrahydro-4-pyridyl)-5-propoxypyrrolo[3,2-b]pyridine (CP 94,253; an agonist of 5-HT(1B) receptors), or SB 216641+CP 94,253; afterwards, on day 10, they received a challenge dose of amphetamine (2.5 mg/kg). In another experiment, mice were given either vehicle or amphetamine (2.5 mg/kg) for 5 days, and were then challenged with amphetamine (2.5 mg/kg) in combination with vehicle, SB 216641, or CP 94,253 on day 10. Locomotor hyperactivity induced by acute administration of amphetamine (day 1) was dose-dependently inhibited by SB 216641 and enhanced by CP 94,253, but not affected by a combination of SB 216641+CP 94,253. The 5-HT(1B) receptor ligands affected similarly the behavioral response to the challenge dose of amphetamine on day 10 (ca. 55-110% more potent than the response to its first administration) when they were combined with the psychostimulant during the development phase (days 1-5) of sensitization. On the other hand, neither SB 216641 nor CP 94,253 administered together with the challenge dose of amphetamine (day 10) affected its behavioral hyperactivity effect in mice treated repeatedly (days 1-5) with the psychostimulant alone. Our results suggest that 5-HT(1B) receptors may play a permissive role in the development, but not expression, of behavioral sensitization, as well as in the acute locomotor response to amphetamine in mice.
Przegalinski
E
E
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Science, 12 Smetna Street, 31-343 Cracow, Poland. przegal@if-pan.krakow.pl
Siwanowicz
J
J
Nowak
E
E
Papla
I
I
Filip
M
M
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001549:Benzamides / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D008024:Ligands; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010069:Oxadiazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013997:Time Factors
D001549:Benzamides; C097067:CP 94253; D000697:Central Nervous System Stimulants; D008024:Ligands; C108531:N-(3-(2-dimethylamino)ethoxy-4-methoxyphenyl)-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-(1,1'-biphenyl)-4-carboxamide; D010069:Oxadiazoles; D011725:Pyridines; D044302:Receptor, Serotonin, 5-HT1B; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D000661:Amphetamine