The effect of serotonin 5HT1B receptor ligands on amphetamine self-administration in rats.
A number of data indicate that serotonin (5-HT) 5-HT(1B) receptor ligands affect the behavioral effects of psychostimulants. In the present study we examined effects of the selective 5-HT(1B) receptor antagonist 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) and the agonist 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride (CP 94253) on amphetamine self-administration in rats. SB 216641 administered in doses of 2.5-7.5 mg/kg did not affect the self-administration of amphetamine injected in unit doses of 0.06 or 0.12 mg/kg/infusion. On the other hand, CP 94253 administered in doses of 2.5 or 5 mg/kg attenuated amphetamine self-administration, yet the effect of 2.5 mg/kg of the agonist was fairly weak and significant only in case of a higher unit dose of the psychostimulant. The inhibitory effect of CP 94253 administered in a dose of 5mg/kg on the self-administration of amphetamine injected in a unit dose of 0.06 mg/kg/infusion was significantly reduced by SB 216641 administrated in a dose of 7.5 mg/kg. These results indicate that tonic activation of 5-HT(1B) receptors is not involved in the self-administration of amphetamine, while pharmacological stimulation of these receptors attenuates this behavioral phenomenon.
Laboratory of Drug Addiction, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Krakow, Poland. kogut@if-pan.krakow.pl
Joanna
J
Miszkiel
Przemysław
P
Adamczyk
Małgorzata
M
Filip
Edmund
E
Przegaliński
D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008024:Ligands; D008297:Male; D010069:Oxadiazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology*; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*
D001549:Benzamides; C097067:CP 94253; 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; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D000661:Amphetamine