Effects of serotonin 5-HT1B receptor ligands on the cocaine- and food-maintained self-administration in rats.
In order to substantiate the concept that cocaine behavioral effects may be influenced by serotonin (5-HT)1B receptors, male Wistar rats were trained to self-administer cocaine intravenously (0.5 mg/kg/injection), and were systemically pretreated with the selective 5-HT1B receptor antagonist N-[3-[3-(dimethylamine)ethoxy]-4-methoxyphenyl]-2'-methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl)-[1,1'-biphenyl]-4-carboxamide hydrochloride (SB 216641), or with the agonist 5-propoxy-3(1,2,3,6-tetrahydro-4-pyridinyl)-1H-pyrrolo[3,2-b]pyridine hydrochloride (CP 94253) before test session during the maintenance phase. The effects of the 5-HT1B receptor ligands on a control reinforcer (food)-induced self-administration and on basal locomotor activity were also assessed. SB 216641 (2.5-7.5 mg/kg) was inactive in altering the cocaine (0.5 mg/kg/injection)-maintained responding and at the highest dose (7.5 mg/kg) it did not alter the self-administration of a cocaine dose on the descending limb of the cocaine (0.125-0.5 mg/kg/injection) dose-effect function. On the other hand, CP 94253 (2.5-7.5 mg/kg) attenuated the cocaine (0.5 mg/kg/injection)-maintained responding with a significant inhibitory effect seen at 7.5 mg/kg, while its doses of 2.5-5 mg/kg potently reduced the self-administration of cocaine (0.125-0.25 mg/kg/injection), in a manner similar to the effect produced by increasing the unit dose of cocaine. The inhibitory effects of CP 94253 (5 mg/kg) on the cocaine (0.125 or 0.25 mg/kg/injection) self-administration were blocked by SB 216641 (7.5 mg/kg). Food reinforcing potential was not altered when either SB 216641 or CP 94253 was given in a dose range between 2.5-7.5 mg/kg. Moreover, none of the 5-HT1B receptor ligands altered horizontal locomotor activity while CP 9253 significantly reduced vertical activity. Our present findings extend previous observations that tonic activation of 5-HT1B receptors is not required for cocaine reinforcement while pharmacological stimulation of 5-HT1B receptors enhances such a property of the psychostimulant. Furthermore, we demonstrated that 5-HT1B receptor agonist-induced enhancement of cocaine reward was independent of an alteration in natural reinforcement.
Przegaliński
Edmund
E
Laboratory of Drug Addiction Pharmacology, Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, 12 Smetna, Poland.
Gołda
Anna
A
Frankowska
Małgorzata
M
Zaniewska
Magdalena
M
Filip
Małgorzata
M
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004435:Eating; D007275:Injections, Intravenous; D008024:Ligands; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010069:Oxadiazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044302:Receptor, Serotonin, 5-HT1B / Q000187:drug effects* / Q000378:metabolism; D012055:Reinforcement Schedule; D012201:Reward; D012646:Self Administration; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D001549:Benzamides; C097067:CP 94253; D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; 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; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D003042:Cocaine