RT Journal Article SR Electronic T1 Regulation of Central Synaptic Transmission by 5-HT1BAuto- and Heteroreceptors JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1271 OP 1278 DO 10.1124/mol.58.6.1271 VO 58 IS 6 A1 Hitoshi Morikawa A1 Olivier J. Manzoni A1 John C. Crabbe A1 John T. Williams YR 2000 UL http://molpharm.aspetjournals.org/content/58/6/1271.abstract AB Although 5-HT1B receptors are believed to be expressed on nerve terminals, their precise mode of action is not fully understood because of the lack of selective antagonists. The 5-HT1B receptor knockout mouse was used in the present investigation to assess the function of 5-HT1B receptors in the modulation of synaptic transmission in three areas of the central nervous system: the dorsal raphe, the ventral midbrain, and the nucleus accumbens. N-(3-Trifluoromethylphenyl)piperazine, a 5-HT1B receptor agonist, potently inhibited 5-HT1A receptor-mediated slow inhibitory postsynaptic potentials (IPSPs) in the dorsal raphe of wild-type but not knockout mice. Both synaptically released 5-HT and exogenous 5-HT caused a presynaptic inhibition that outlasted the postsynaptic hyperpolarization only in wild-type mice. In the ventral midbrain, 5-HT1B receptor-dependent inhibition of γ-aminobutyric acidB IPSPs in dopamine neurons was present in wild-type animals and absent in knockout animals. Similar results were obtained in the nucleus accumbens measuring glutamate-mediated excitatory postsynaptic currents in medium spiny neurons. Finally, cocaine, which blocks 5-HT uptake, inhibited IPSPs in the dorsal raphe and the ventral midbrain of wild-type but not knockout mice, whereas cocaine produced comparable inhibition of excitatory postsynaptic currents in the nucleus accumbens of both types of animals. These results indicate that 5-HT1B receptors function as autoreceptors and heteroreceptors to exert presynaptic inhibition of transmitter release in the central nervous system. Furthermore, this study underscores the role played by presynaptic 5-HT1B receptors in mediating the effects of cocaine on synaptic transmission.