EXCITATION OF RAT SUBSTANTIA-NIGRA PARS RETICULATA NEURONS BY 5-HYDROXYTRYPTAMINE IN-VITRO - EVIDENCE FOR A DIRECT ACTION MEDIATED BY 5-HYDROXYTRYPTAMINE(2C) RECEPTORS
Ce. Rick et al., EXCITATION OF RAT SUBSTANTIA-NIGRA PARS RETICULATA NEURONS BY 5-HYDROXYTRYPTAMINE IN-VITRO - EVIDENCE FOR A DIRECT ACTION MEDIATED BY 5-HYDROXYTRYPTAMINE(2C) RECEPTORS, Neuroscience, 69(3), 1995, pp. 903-913
Single-unit extracellular and whole-cell patch clamp recording were us
ed to study the actions of exogenously applied 5-hydroxytryptamine on
substantia nigra pars reticulata neurons in parasaggital slices of rat
midbrain. Seventy-six per cent of substantia nigra pars reticulata ce
lls (254/334) recorded extracellularly were excited by 5-hydroxytrypta
mine (EC(50) = 9.56 mu M); in the remainder, inhibitions (13.5%), biph
asic responses (4.2%) or lack of response (6.3%) were observed. Using
whole-cell patch recording, 5-hydroxytryptamine (10 mu M) caused eithe
r an inward current (9/9 cells) or a depolarization (3/3 cells) at mem
brane potentials in the range -50 to -90 mV, which was resistant to te
trodotoxin (4/4 cells), indicating that the predominant, excitatory ac
tion of 5-hydroxytryptamine was due to a direct action on substantia n
igra pars reticulata neurons. The 5-hydroxytryptamine excitation (reco
rded extracellularly) was reduced to 24 +/- 6% of control values by me
thysergide (0.1 mu M) and to 17 +/- 5% of control by ketanserin (1O mu
M), but was unaffected by the 5-hydroxytryptamine antagonists spipero
ne (0.1 mu M), yohimbine (O.l mu M), pindolol (1 mu M), GR113808A (1 m
u M) or ICS 205930 (10 mu M). In addition, the 5-hydroxytryptamine exc
itation was mimicked by the 5-hydroxytryptamine(2C) receptor-preferrin
g agonist oc-methyl 5-hydroxytryptamine (10 mu M), but the agonists CP
93,129 (0.1-1 mu M) and(+/-)-2-dipropylamino-8-hydroxy-1 ,2,3,4-tetrah
ydronaphthalene hydrobromide (0.1-1 mu M) were without effect. Taken t
ogether, this pharmacology indicated involvement of the 5-hydroxytrypt
amine(2C) receptor in the 5-hydroxytryptamine excitation, while other
candidate receptors known to be present in rat substantia nigra pars r
eticulata (5-hydroxytryptamine(1B), 5-hydroxytryptamine(2A) and 5-hydr
oxytryptamine(4)) could be excluded from consideration. While in accor
d with current information on the location of 5-hydroxytryptamine rece
ptor subtypes in substantia nigra pars reticulata, and the consequence
of activation of neuronal 5-hydroxytryptamine(2C) receptors, these re
sults contrast with data from in vivo experiments which suggest that t
he net effect of 5-hydroxytryptamine is to inhibit substantia nigra pa
rs reticulata neurons. The reason for this apparent discrepancy may li
e in detailed consideration of the microcircuitry of the substantia ni
gra pars reticulata. This may lead to a re-evaluation of the influence
of 5-hydroxytryptamine on this basal ganglia output relay nucleus, an
d its role in motor control and the gating of generalized seizure acti
vity.