PT  - JOURNAL ARTICLE
AU  - Hitoshi Morikawa
AU  - Olivier J. Manzoni
AU  - John C. Crabbe
AU  - John T. Williams
TI  - Regulation of Central Synaptic Transmission by 5-HT<sub>1B</sub>Auto- and Heteroreceptors
AID  - 10.1124/mol.58.6.1271
DP  - 2000 Dec 01
TA  - Molecular Pharmacology
PG  - 1271--1278
VI  - 58
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/58/6/1271.short
4100  - http://molpharm.aspetjournals.org/content/58/6/1271.full
SO  - Mol Pharmacol2000 Dec 01; 58
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.