Local Dopaminergic Modulation of the Motor Activity Induced by N-methyl-D-aspartate Receptor Stimulation in the Ventral Hippocampus

Abstract

Dopaminergic neurotransmission has been implicated in the motor activating effects induced by the local infusion of NMDA in the ventral hippocampus (VH). The nucleus accumbens and the ventral tegmental area (VTA) have been proposed to be the main loci where dopamine is acting as a positive modulator of the VH NMDA receptor-mediated motor activating effects. However, the existence of a relatively high dopamine innervation and dopamine receptor density in the VH suggests the possibility of local dopamine/NMDA receptor interactions. This hypothesis was tested by studying the effects of the bilateral local VH infusion of NMDA (0.05, 0.1, 0.5 and 1.0 g/side), the dopamine D1/D5 receptor antagonist SCH 23390 (1 g/side) and the dopamine D2 receptor antagonist raclopride (1 and 5 g/side). Neither SCH 23390 nor raclopride induced any significant change in motor activity compared with the vehicle control group, but both compounds significantly antagonized the motor activation induced by NMDA. SCH 23390 (1 g/side) was more potent that raclopride (minimal effective dose: 5 g/side). These results demonstrate the existence of a strong tonic facilitating effect of dopamine, acting preferentially at dopamine D1/D5 receptors, on NMDA receptor-mediated effects in the VH.

Hippocampal Dopamine Receptors Modulate the Motor Activation and the Increase in Dopamine Levels in the Rat Nucleus Accumbens Evoked by Chemical Stimulation of the Ventral Hippocampus

“…Giménez-Llort et al (2002) showed that SCH 23390 and raclopride microinjected locally into the VH significantly antagonized the motor activation evoked by simultaneous microinjections of NMDA; as occurred in our study, neither raclopride nor SCH 23390 induced any significant change in motor activity compared with the control group. Consistent with our data, these authors also reported that, apparently, in terms of attenuating NMDA-evoked activation SCH 23390 was more powerful than raclopride.…”

“…However, until recently, the effects of this modulation have not been found in vivo. A recently published study shows that DA neurotransmission in VH is clearly involved in controlling the locomotor responses to NMDA stimulation (Giménez-Llort et al, 2002). Bilateral local VH infusion of either the dopamine D1/D5 receptor antagonist SCH 23390 or the dopamine D2 receptor antagonist raclopride significantly antagonized the motor activation induced by NMDA, SCH 23390 was found to be more potent than raclopride.…”

“…Local infusions of N-methyl-D-aspartate (NMDA) in the ventral hippocampus (VH) have been found to elicit locomotor activation in rodents (Yang and Mogenson, 1987;Wu and Brudzynski, 1995;Brudzynski and Gibson, 1997;Bardgett and Henry, 1999;Legault and Wise, 1999;Giménez-Llort et al, 2002). Similarly, NMDA infusion in the VH also induces robust and sustained increases in extracellular dopamine (DA) levels in the nucleus accumbens (NAc) of rats, which are apparently correlated with the time course of increased locomotor activity (Brudzynski and Gibson, 1997;Legault and Wise, 1999;Legault et al, 2000;Floresco et al, 2001;Cano-Cebrián et al, 2003).…”

Fluvastatin Alters Psychomotor Performance and Daily Activity but not the Spatial Memory in Rats

“…This is caused by apoptosis in differentiated human skeletal muscle cells (Sacher et al 2005) or statin affected NMDA receptor functions. Local dopaminergic modulation of the motor activity induced by NMDA receptor stimulation in the ventral hippocampus was shown by Gimenez-Llort (2002).…”

Dopamine D2 receptor plays a role in memory function: implications of dopamine–acetylcholine interaction in the ventral hippocampus

“…Therefore, we concluded that the ameliorative effect of the D 2 R agonist on mnemonic impairment did not improve locomotor activity, which would be expected when a dopaminergic agonist is administered systemically (Millan et al 2004). Moreover, Gimenez-Llort et al (2002) also showed that local raclopride administration to the ventral hippocampus induced no significant changes in locomotor activity.…”