The effect of drugs interacting with serotonergic 5HT3 and 5HT4 receptors on morphine place conditioning.
The effect of 5HT3 and 5HT4 active compounds on the motivational properties of morphine has been examined in the place conditioning (PC) paradigm using unbiased procedure. Place conditioning with morphine produced significant place preference. Pretreatment with the DAU 6285 (mixed 5HT3 antagonist--5HT4 antagonist) abolished morphine-induced PC. Ondansetron (selective 5HT3 antagonist) attenuated morphine place preference at the dose of 0.1 mg/kg. BIMU 8 (mixed 5HT3 antagonist--5HT4 agonist) failed to modify morphine PC in the 0.001-0.1 mg/kg dose range. While ondansetron given alone failed to produce place conditioning, pairing of BIMU 8 (0.001 mg/kg) induced significant place preference. On the other hand, animals were frequently avoiding compartment paired with the injection of DAU 6285. These findings suggest that 5-hydroxytryptamine by means of 5HT4 receptors mediates appetitive properties of morphine induced-stimuli and suggest that 5HT4 receptor may be involved in the brain reward and reinforcement processes.
Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, Warszawa, Poland.
A
A
Bisaga
J
J
Sikora
W
W
Kostowski
D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003216:Conditioning, Operant / Q000187:drug effects*; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D017294:Ondansetron / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012054:Reinforcement, Psychology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D001562:Benzimidazoles; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C074390:DAU 6285; C070189:(endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide; D017294:Ondansetron; D009020:Morphine