Effects of amphetamine on the release of excitatory amino acid neurotransmitters in the basal ganglia of the conscious rat

Abstract

The effects of systemic injections of amphetamine sulfate on the release of aspartic acid, glutamic acid, and glutamine were studied using a push-pull perfusion system in the conscious rat. Amphetamine produced a dose-related increase of the extracellular levels of aspartic acid and glutamic acid. The mean time effect of amphetamine was 40 min, followed by a recovery to baseline levels. The mean percentage increase in amino acids released by the highest dose of amphetamine (5 mg/kg) was as follows: Asp, 334.6%; Glu, 224.5%; and Gln, 317.6%. All these effects were blocked by the dopamine D1-D2 receptor blocker haloperidol. It is suggested that dopamine, released by amphetamine, induces the release of amino acid neurotransmitters in the neostriatum. In addition, it is proposed that dopamine could mediate the neurotoxic effects produced by amphetamines through their secondary action on the release of excitatory amino acids.

Rhynchophylline down-regulates NR2B expression in cortex and hippocampal CA1 area of amphetamine-induced conditioned place preference rat

“…Since the dopamine receptor blocker is protective for amphetamine induced amino acid neurotransmitters release (Mora and Porras, 1993) and the selective serotonin uptake inhibitor is protective for amphetamine induced 5-HT depletion (Schmidt, 1987), the current study showed amphetamine-induced enhancement in mRNA levels of glutamatergic NMDA receptor subunits may contribute to amphetamine mediated neurotoxic effects. Furthermore, there are similarities between the immediate effects of amphetamine analogue administration and other drugs of abuse.…”

Amphetamine Modulates Excitatory Neurotransmission through Endocytosis of the Glutamate Transporter EAAT3 in Dopamine Neurons

“…In fact, vGLUT2-mediated glutamate release from DA neurons has been found to be essential to AMPH-mediated behavioral responses (Birgner et al, 2009). Elevations in extracellular glutamate concentrations after AMPH treatment have been observed in the striatum (Del Arco et al, 1999; Mora and Porras, 1993), nucleus accumbens (Dalia et al, 1998; Xue et al, 1996) and prefrontal cortex (Del Arco et al, 1998) supporting a role for AMPH-mediated EAAT3 modulation at post-synaptic targets of DA and glutamate release from dopaminergic neurons. Indeed, our biotinylation data addressing EAAT3(+) processes in slices more rostral to the midbrain suggests that AMPH-mediated endocytosis also occurs in terminal fields of DA projections (Figure S2C).…”

“…Although DA itself is clearly important for these actions, recent work underscores the importance of changes in glutamatergic signaling after AMPH treatment as well (Reissner and Kalivas, 2010; Wolf and Ferrario, 2010). For example, AMPH increases extracellular glutamate in various brain regions including the striatum, VTA and NAc (Del Arco et al, 1999; Kim et al, 1981; Mora and Porras, 1993; Xue et al, 1996), but it has not been established whether this change can be explained by increased synaptic release or by reduced clearance of glutamate. In vivo microdialysis studies indicate that the increases in extracellular glutamate are calcium independent (Del Arco et al, 1999; Del Arco et al, 1998; Xue et al, 1996) suggesting that synaptic release does not fully account for the observed increases in extracellular glutamate concentrations.…”

Amphetamine increases the phosphorylation of neuromodulin and synapsin I in rat striatal synaptosomes

“…Possibilities include dopamine, other monoamines such as norepinephrine and serotonin, glutamate, or even neuropeptides. AMPH-mediated release of some substances in rat striatum, such as glutamate (Mora and Porras, 1993), is mediated by released DA. Our studies with DA antagonists suggest that DA may not mediating the increases in synapsin or NM phosphorylation, although there was some effect of the D1 antagonist SCH23390 on synapsin I phosphorylation.…”

“…Small, clear vesicles and synapsin I are prominent in glutamatergic synaptosomes (Verhage et al, 1994). There appear to be interactions between dopaminergic and glutamatergic nerve terminals in striatum in that glutamate and DA may alter each other's release (Maura et al, 1988;Mora and Porras, 1993; and see references in Finnegan and Taraska, 1996). Low concentrations of DA suppressed the K 1 -induced release of glutamate in a presynaptic-inhibitory manner through dopamine D2 receptors on glutaminergic terminals innervated from cerebral cortex (Maura et al, 1988).…”