5-hydroxytryptamine1B receptors block the GABAB synaptic potential in rat dopamine neurons

Abstract

Intracellular recordings were made from presumed dopamine-containing neurons in slices cut from the midbrain of the rat. Focal electrical stimulation produced a hyperpolarizing synaptic potential that was reduced by 75-95% by the GABAB-receptor antagonist 2-hydroxysaclofen (300 microM). 5-HT (3-100 microM) reduced the amplitude of the GABAB synaptic potential by 20-74%, with a 50% reduction at 10 microM, but did not reduce the amplitude of synaptic potentials mediated by GABAA receptors. 5-HT acted presynaptically because hyperpolarizations produced by exogenously administered GABA (1 mM) in picrotoxin (100 microM) were not affected by 5-HT (30 microM). (+/-)-Cyanopindolol (100 nM), a 5-HT1B antagonist, blocked the effect of 5-HT (10 microM); spiperone (1 microM), which is an antagonist at 5-HT1A and 5-HT2 receptors, had no effect. The amplitude of the GABAB synaptic potential was reduced by the 5-HT1B receptor agonists 1-[3-(trifluoromethyl)-phenyl]-piperazine (300 nM) and 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)-pyrrolo[1,2-a]quinoxaline (1 microM), but not by the 5-HT1A agonist N,N-dipropyl-5-carboxamidotryptamine (1 microM) or the 5-HT2 agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane (10 microM). We conclude that 5-HT activates presynaptic 5-HT1B receptors that inhibit the release of GABA onto GABAB but not GABAA receptors.

5-HT inhibits synaptic transmission in rat subthalamic nucleus neurons in vitro

“…Mismatches between mRNA and binding sites reveal that 5HT 1B and 5HT 1D receptors are expressed predominantly on nerve terminals (Boschert et al, 1994;Maroteaux et al, 1992). Consistent with its presynaptic location, 5HT 1B receptor activation has been shown to cause presynaptic inhibition of glutamate-mediated EPSCs in many brain regions such as the hypoglossal nucleus (Singer et al, 1996) and nucleus accumbens (Muramatsu et al, 1998), and to inhibit GABA-mediated transmission in structures such as the dorsolateral septum (Matsuoka et al, 2004) and substantia nigra (Johnson et al, 1992;Stanford and Lacey, 1996). Results of the present study clearly show that 5HT 1B receptor activation also causes presynaptic inhibition of transmission in the STN.…”

Pharmacologic mechanisms of serotonergic regulation of dopamine neurotransmission

“…Supporting this circuitry, administration of the 5-HT1B agonist CP 93129 inhibits high-potassium-induced [ 3 H]GABA release from VTA slices (Yan and Yan, 2001b). Additionally, work in rat and guinea pig slices of the VTA has shown that the application of 5-HT or a 5-HT1B agonist reduces the amplitude of GABA-B IPSPs in DA neurons (Johnson et al, 1992;Williams, 1994, 1995). Coadministration of a 5-HT1B antagonist blocked the inhibitory effect of 5-HT on the GABA-B IPSP (Johnson et al, 1992;Cameron and Williams, 1995), while spiperone, an antagonist for 5-HT1A/2 receptors, did not (Johnson et al, 1992).…”

“…Additionally, work in rat and guinea pig slices of the VTA has shown that the application of 5-HT or a 5-HT1B agonist reduces the amplitude of GABA-B IPSPs in DA neurons (Johnson et al, 1992;Williams, 1994, 1995). Coadministration of a 5-HT1B antagonist blocked the inhibitory effect of 5-HT on the GABA-B IPSP (Johnson et al, 1992;Cameron and Williams, 1995), while spiperone, an antagonist for 5-HT1A/2 receptors, did not (Johnson et al, 1992). Some investigators propose that the relevant 5-HT1B heteroreceptors are located on the axon terminals of GABAergic projection neurons from the NA (O'Dell and Yan and Yan 2001a).…”

Electrophysiologic Changes in Ventral Midbrain Dopaminergic Neurons Resulting from (+/−) -3,4-Methylenedioxymethamphetamine (MDMA—“Ecstasy”)

“…A typical effect caused by an increased serotoninergic tone in the ventral midbrain is a depression of the GABA B postsynaptic potential on the DAergic neurons (Cameron and Williams 1994;Johnson et al 1992). Accordingly, MDMA (10 mol/L) reversibly diminished the amplitude of the GABA B inhibitory potential by 49.5% Ϯ 7 % (n ϭ 4, p Ͻ .05), and this effect was antagonized by pindolol (300 nmol/L; n ϭ 4, p Ͻ .05; Figure 5).…”