Real‐time measurement of stimulated 5‐hydroxytryptamine release in rat substantia nigra pars reticulata brain slices

Abstract

Fast cyclic voltammetry at a carbon fibre microelectrode was used to measure 5-HT signals following electrical or chemical stimulation in rat substantia nigra pars reticulata slices. Chemical stimulation with (+)-amphetamine or veratrine gave signals which were indistinguishable from those of exogenous 5-HT. Electrical stimulation of sufficient duration gave voltammetric signals which were characteristic of 5-HT. Release of dopamine was not detected following either chemical or electrical stimulation. The 5-HT signals were attenuated by TTX and enhanced by fluvoxamine. It was not possible to demonstrate regulation of 5-HT release in the SNr by 5-HT1B autoreceptors using CGS 12066A or methiothepin. Signal following electrical stimulation were not enhanced by either benztropine or GBR12909, or modified in the presence of either quinpirole or sulpiride. We conclude that 5-HT release can be detected voltammetrically in the SNr; 5-HT release is likely to be from axon terminals, but somatodendritic DA release could not be detected.

Histamine H3Receptors Inhibit Serotonin Release in Substantia Nigra Pars Reticulata

“…The evoked neurotransmitter release detected in the SNr in this study was Na V ϩ and Ca 2ϩ dependent and sensitive to depolarization frequency and pulse number, as previously reported for 5-HT exocytosis in the SNr (O'Connor and Kruk, 1991;Iravani and Kruk, 1997;Bunin et al, 1998). It is well established that 5-HT is the predominant monoamine detected by FCV at CFMs in the rat SNr (Cragg et al, 1997b;Iravani and Kruk, 1997;Bunin et al, 1998); this differs from the guinea pig SNr in which 5-HT is detected far less frequently and DA predominates (Cragg et al, 1997b).…”

“…3E) ( post hoc Dunnett's t tests vs 10 Hz: 20 -100 Hz, p Ͻ 0.001-0.05; 200 Hz, p Ͼ 0.05). Mean peak-evoked [5-HT] o varied significantly with the number of pulses in a train (100 Hz; one-way ANOVA; p Ͻ 0.001) as observed previously (Iravani and Kruk, 1997;Bunin et al, 1998), showing a linear dependence at pulse numbers Ͻ30 (Fig. 3F ) (linear regression over 0 -30 pulses; y-intercept ϭ 0; R 2 ϭ 0.97).…”

“…2 D) by the characteristic doublereduction current profile for 5-HT as noted previously in SNr (Davidson and Stamford, 1996;Cragg et al, 1997b;Iravani and Kruk, 1997;Bunin et al, 1998). Furthermore, it has been identified previously that the primary substance detected in rat SNr using this method is 5-HT and not DA (Cragg et al, 1997b;Iravani and Kruk, 1997;Bunin et al, 1998).…”

“…Bath application of the SERT inhibitor citalopram (75 nM) prolonged the extracellular lifetime of 5-HT and significantly enhanced (Fig. 3A) (M-WU; p Ͻ 0.001; n ϭ 28) as shown previously with SERT inhibitors in the SNr (Iravani and Kruk, 1997;Bunin et al, 1998). Conversely, application of the DAT inhibitor GBR 12909 (1 M) had no effect on the lifetime or peak concentration of the detected substance, 5-HT (Fig.…”

“…It is well established that 5-HT is the predominant monoamine detected by FCV at CFMs in the rat SNr (Cragg et al, 1997b;Iravani and Kruk, 1997;Bunin et al, 1998); this differs from the guinea pig SNr in which 5-HT is detected far less frequently and DA predominates (Cragg et al, 1997b). Several lines of evidence indicate that the signal monitored in this study was indeed caused by the release of 5-HT.…”