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.
|Number of pages||1|
|Publication status||Published - 2002|
|Event||Thirty-Second Annual Meeting of the Society for Neuroscience - Orlando, USA|
Duration: 2 Nov 2002 → 7 Nov 2002
|Conference||Thirty-Second Annual Meeting of the Society for Neuroscience|
|Period||2/11/02 → 7/11/02|