Crucial role of the 5-HT2C receptor, but not of the 5-HT2A receptor, in the down regulation of stimulated dopamine release produced by pressure exposure in freely moving rats.
Helium pressure of more than 2 MPa is a well known factor underlying pressure-dependent central neuroexcitatory disorders, referred to as the high-pressure neurological syndrome. This includes an increase in both serotonin (5-HT) and dopamine (DA) release. The relationship between the increase in 5-HT transmission produced by helium pressure and its effect on DA release has been clarified in a recent study, which have first demonstrated that the helium pressure-induced increase in DA release was dependent on some 5-HT receptor activation. In the present study, we examined in freely moving rats the role of 5-HT2A and 5-HT2C receptors in the increase in DA release induced by 8 MPa helium pressure. We used the 5-HT2A receptor antagonist ketanserin and the 5-HT2C receptor agonist m-CPP which have been demonstrated to reduce DA function. Because neither ketanserin is an ideal 5-HT2A receptor antagonist nor m-CPP an ideal 5-HT2C receptor agonist, additional experiments were made at normal pressure to check up on the selectivity of ketanserin and m-CPP for 5-HT2A and 5-HT2C receptors, respectively. Administration of m-CPP reduced both DA basal level and the helium pressure-induced increase in DA release, whereas administration of ketanserin only showed a little effect on the increase in DA release produced by high helium pressure. These results suggest that the 5-HT2C receptor, but not the 5-HT2A receptor, would play a crucial role in the helium pressure-induced increase in DA release. This further suggests that helium pressure may simultaneously induce an increase in 5-HT transmission at the level of 5-HT2A receptors and a decrease in 5-HT transmission at the level of 5-HT2C receptors.
Laboratoire de Neurosciences Cellulaires et Intêgratives, Faculté des Sciences, Université Nancy 1, France.
B
B
Kriem
J C
JC
Rostain
J H
JH
Abraini
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004563:Electrochemistry / Q000379:methods; D006371:Helium; D006610:High Pressure Neurological Syndrome / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D010879:Piperazines / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000502:physiology*
D010879:Piperazines; D011985:Receptors, Serotonin; D006371:Helium; D007650:Ketanserin; C015068:1-(3-chlorophenyl)piperazine; D004298:Dopamine