Matthew J. During

Dopamine release in rat striatum - Physiological coupling to tyrosine supply

Abstract: Intracerebral microdialysis was used to monitor dopamine release in rat striatal extracellular fluid following the intraperitoneal administration of dopamines precursor amino acid, l‐tyrosine. Dopamine concentrations in dialysates increased transiently after tyrosine (50–100 mg/kg) administration. Pretreatment with haloperidol or the partial lesioning of nigrostriatal neurons enhanced the effect of tyrosine on dopamine release, and haloperidol also prolonged this effect. These data suggest that nigrostriatal dopaminergic neurons are responsive to changes in precursor availability under basal conditions, but that receptor‐mediated feedback mechanisms limit the magnitude and duration of this effect.

Effects of systemicl-tyrosine on dopamine release from rat corpus striatum and nucleus accumbens

Intracerebral dialysis was used to monitor extracellular fluid from rat striatum and nucleus accumbens following the intraperitoneal administration of tyrosine. Dopamine concentrations in dialysates from both the striatum and the nucleus accumbens increased significantly in response to the tyrosine. The magnitude of the tyrosine effect was greater in the nucleus accumbens than in the striatum. Hence, mesolimbic dopaminergic neurons may be especially responsive to precursor availability.

Tyrosine: effects on catecholamine release.

Tyrosine administration elevates striatal levels of dopamine metabolites in animals given treatments that accelerate nigrostriatal firing, but not in untreated rats. We examined the possibility that the amino acid might actually enhance dopamine release in untreated animals, but that the technique of measuring striatal dopamine metabolism was too insensitive to demonstrate such an effect. Dopamine release was assessed directly, using brain microdialysis of striatal extracellular fluid. Tyrosine administration (50-200 mg/kg IP) did indeed cause a dose related increase in extracellular fluid dopamine levels with minor elevations in levels of DOPAC and HVA, its major metabolites, which were not dose-related. The rise in dopamine was short-lived, suggesting that receptor-mediated feedback mechanisms responded to the increased dopamine release by diminishing neuronal firing or sensitivity to tyrosine. These observations indicate that measurement of changes in striatal DOPAC and HVA, if negative, need not rule out increases in nigrostriatal dopamine release.

Phenylalanine administration influences dopamine release in the rat's corpus striatum

We used intracerebral dialysis to monitor extracellular levels of dopamine and its major metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in rat striatum. Levels of these compounds were determined after intraperitoneal administration of phenylalanine (200, 500 and 1000 mg/kg). A dose of 200 mg/kg phenylalanine increased basal dopamine release by 59%, peaking at 75 min. There was no change in basal dopamine release after the 500 mg dose, whereas the 1000 mg/kg dose significantly reduced (26%) dopamine release. No significant changes were observed in the concentrations of DOPAC and HVA with any of the treatments, indicating that changes in brain phenylalanine and tyrosine levels may selectively affect production of the dopamine molecules that are preferentially released into synapses.

Pprocesses That Couple Amino Acid Availability to Neurotransmitter Synthesis and Release

Certain neurotransmitters are synthesized from precursor amino acids (e. g. catecholamines from tyrosine; serotonin [5-hydroxytryptamine or 5HT] from tryptophan) which must be obtained from the circulation. The concentrations of tyrosine and tryptophan, as well as of the other large neutral amino acids (LNAA) in plasma, are subject to wide variations (1, 2), changing not only when people or animals receive various drugs (3, 4) or the amino acids themselves (5, 6), but also in disease states affecting amino acid metabolism (7, 8), and, of major physiological relevance, in association with eating (1, 2) or with strenuous exercise (9, 10, 11). As will be described below, these variations often cause parallel changes in the levels of these amino acids within the monoaminergic neurons, and thereby may influence both neurotransmitter synthesis and even central neurotransmission (12).

An In Vivo Study of Dopamine Release in Striatum: The Effects of Phenylalanine

We used intracerebral dialysis to monitor extracellular levels of dopamine and its major metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum of chloralose/urethane-anesthetized rats. Levels of these compounds were determined after intraperitoneal administration of phenylalanine (200, 500, and 1000-mg/kg). A dose of 200 mg phenylalanine per kg (which increases brain tyrosine by more than phenylalanine) increased basal dopamine release by 59%, peaking at 75 min. There was no change in basal dopamine release after the 500-mg dose, whereas the 1000-mg/kg dose (which increases brain phenylalanine more than tyrosine) significantly reduced (26%) dopamine release. No corresponding changes were observed in the concentrations of DOPAC and HVA with any of the treatments, indicating that changes in brain phenylalanine and tyrosine levels may selectively affect production of the dopamine molecules that are preferentially released into synapses.