Ipsapirone enhances the dopamine outflow via 5-HT1A receptors in the rat prefrontal cortex.
In the present study, we investigated both the effect of ipsapirone on the dopamine outflow and its selectivity towards 5-HT1A receptors in the rat prefrontal cortex. Using a brain microdialysis method in freely moving animals, it was found that ipsapirone, 5 and 10 mg/kg dose-dependently enhanced the outflow of dopamine, while 2.5 mg/kg was ineffective. The above effects of ipsapirone were mimicked by buspirone (2.5 and 5 mg/kg), another 5-HT1A receptor agonist, but not 1-PP (1-pyrimidinylpiperazine, 5 mg/kg)-a centrally active metabolite of ipsapirone. The effect of ipsapirone (10 mg/kg) on the dopamine outflow in the rat prefrontal cortex was antagonized by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl]piperazine (NAN-190, 1 mg/kg) and (N-tert-butyl-3-(4-(2-methoxyphenylpiperazin-1-yl)-2- phenylpropionamide (WAY 100135, 10 mg/k.g.), i.e. substances with agonistic/antagonistic and antagonistic properties in relation to 5-HT1A receptors, respectively. NAN-190 (1 mg/kg) enhanced the outflow of dopamine, while WAY 100135 (10 mg/kg) failed to alter it. It is concluded that 5-HT1A receptor agonists may be involved in the regulation of dopaminergic neurotransmission in the rat prefrontal cortex and may have therapeutic potential in the treatment of disorders associated with dysfunction of the mesocortical dopaminergic system.
Wedzony
K
K
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland. nfwedzon@cyf-kr.edu.pl
Maćkowiak
M
M
Fijał
K
K
Gołembiowska
K
K
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000818:Animals; D002065:Buspirone / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000032:analysis; D008297:Male; D017551:Microdialysis; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D010879:Piperazines; D011743:Pyrimidines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D015102:3,4-Dihydroxyphenylacetic Acid; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C081293:WAY 100135; C043077:ipsapirone; D002065:Buspirone; D004298:Dopamine; D006719:Homovanillic Acid