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 p ressure-dependent central neuroexcitatory disorders, referred to as th e high-pressure neurological syndrome. This includes an increase in bo th serotonin (5-HT) and dopamine (DA) release. The relationship betwee n the increase in 5-HT transmission produced by helium pressure and it s effect on DA release has been clarified in a recent study, which hav e first demonstrated that the helium pressure-induced increase in DA r elease 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 press ure. We used the 5-HT2A receptor antagonist ketanserin and the 5-HT2C receptor agonist m-CPP which have been demonstrated to reduce DA funct ion. Because neither ketanserin is an ideal 5-HT2A receptor antagonist nor m-CPP an ideal 5-HT2C receptor agonist, additional experiments we re made at normal pressure to check up on the selectivity of ketanseri n and m-CPP for 5-HT2A and 5-HT2C receptors, respectively. Administrat ion of m-CPP reduced both DA basal level and the helium pressure-induc ed increase in DA release, whereas administration of ketanserin only s howed a little effect on the increase in DA release produced by high h elium pressure. These results suggest that the 5-HT2C receptor, but no t the 5-HT2A receptor, would play a crucial role in the helium pressur e-induced increase in DA release. This further suggests that helium pr essure may simultaneously induce an increase in 5-HT transmission at t he level of 5-HT2A receptors and a decrease in 5-HT transmission at th e level of 5-HT2C receptors. (C) 1998 Elsevier Science B.V. All rights reserved.