| 11093763 |
Morikawa H, Manzoni OJ, Crabbe JC, Williams JT: Regulation of central synaptic transmission by 5-HT (1B) auto- and heteroreceptors. Mol Pharmacol. 2000 Dec;58(6):1271-8.
Although 5-HT (1B) 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-HT (1B) receptor knockout mouse was used in the present investigation to assess the function of 5-HT (1B) 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-HT (1B) receptor agonist, potently inhibited 5-HT (1A) 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-HT (1B) receptor-dependent inhibition of gamma-aminobutyric acid (B) 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-HT (1B) 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-HT (1B) receptors in mediating the effects of cocaine on synaptic transmission. |
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