Cortex-elicited long-term depression in midbrain dopamine cells

functional consequences on striatal dopamine release

Charles Blaha, Melanie Webb, Andrea Fogarty, Jeffery Wickens

    Research output: Contribution to conferenceAbstract


    Recent in vitro electrophysiological studies have shown that long-term depression (LTD) can be induced in midbrain dopamine (DA) cells by applying a tetanising electrical stimulus (TES) to excitatory glutamatergic (Glu) inputs near the substantia nigra (SN) (Jones et al./Thomas et al., J Neurosci, 20, 2000). Also, bath applied amphetamine (AMP) or a D2 dopamine receptor agonist (QUIN, quinpirole), but not NMDA (APV) or metabotropic (MCPG) Glu receptor antagonists, blocks LTD induction in DA cells. In this study, striatal DA release in urethane (1.8g/kg) anesthetized male rats was monitored in real-time (sub-msec samples) at carbon fibre microelectrodes using fixed potential amperometry (FPA). For the first time in vivo we show that electrical stimulation (1-15 pulses, 50Hz) of Glu cells in the prefrontal cortex (PFC) projecting to the SN evokes a transient increase in DA release. These PFC-evoked responses were attenuated by ~50% following TES of the PFC. Consistent with in vitro data, intra-SN infusions of AMP (5µg/µl), QUIN (10µg/µl), or scopolamine (100µg/µl) blocked the TES-induced attenuations in PFC-evoked DA release. Intra-SN infusions of APV (0.1µg/µl) or MCPG (2µg/µl) were without effect. The data suggest that LTD is an important compensatory mechanism of excitatory control of central dopamine systems that may be compromised by exposure to psychostimulant drugs. Overall, results demonstrate the utility of in vivo FPA to study the functional consequences of synaptic plasticity in midbrain DA cells on forebrain DA neurotransmission.
    Original languageEnglish
    Number of pages1
    Publication statusPublished - 2002
    EventThirty-Second Annual Meeting of the Society for Neuroscience - Orlando, USA
    Duration: 2 Nov 20027 Nov 2002


    ConferenceThirty-Second Annual Meeting of the Society for Neuroscience
    CityOrlando, USA

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