Effect of serotonergic agents on adenosine A2 receptor mediated catalepsy in mice

The effect of serotonergic agents was studied on the adenosine A₂ receptor agonist NECA-induced catalepsy in mice. The 5-HT releaser fenfluramine, the 5-HT_1A agonist 8-OH-DPAT, the 5-HT_2A/1C receptor agonist DOI and the 5-HT_2A/1C receptor antagonists ketanserin and mianserin reversed NECA-induced catalepsy. p-MPPI and ketanserin reversed the anticataleptic actions of 8-OH-DPAT and DOI, respectively. Further, the 5-HT reuptake inhibitor fluoxetine, the 5-HT_1B/1C receptor agonist TFMPP, the 5-HT synthesis inhibitor p-CPA, the selective 5-HT_1A receptor antagonist p-MPPI, the 5-HT_1A/1B receptor antagonist pindolol and the 5-HT₃ receptor antagonist LY 278, 584 had no effect on NECA-induced catalepsy. The anticataleptic action of fenfluramine was not affected by pretreatment with p-CPA. In p-CPA treated rats, ketanserin did not affect the anticataleptic effect of fenfluramine, whereas p-MPPI partially reversed this effect. It is concluded that modulation of serotonergic neurotransmission at 5-HT_1A and 5-HT_2A/1C receptors affects the cataleptic action of experimental antipsychotic agents with adenosine A₂ receptor agonistic activity. Received: 5 May 1997/Final version: 2 September 1997