Significance of dopamine metabolites in the evaluation of drugs acting on dopaminergic neurons. Eur J Pharmacol
Institute of Pharmacology, School of Medicine, University of Milan, Via Vanvitelli 32, Milan, Italy European Journal of Pharmacology
(Impact Factor: 2.53).
12/1978; 52(2):201-7. DOI: 10.1016/0014-2999(78)90207-8
The effect of various drugs was studied on 3-methoxytyramine (3-MT) concentrations in rat striatum. The drugs were chosen for their ability to interfere with the dopaminergic system at different levels. Dopamine (DA) acidic metabolites, i.e. homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), were also measured. Changes of 3-MT, unlike those of DOPAC and HVA, seem to reflect the functional activity of dopaminergic neurons. In fact drugs believed to increase or decrease DA content in the synaptic cleft produce predictable changes of striatal 3-MT. Thus cocaine, nomifensine and d-amphetamine increase 3-MT concentrations while gamma-butyrolactone, alpha-methyltyrosine and apomorphine decrease it.
Available from: Romana Šlamberová
- "First, our results showed that prenatal MA exposure did not affect the nociception in adulthood. There are no previous data on MA, so our results could be compared to the data examining the effect of prenatal exposure to cocaine, because it acts in similar way as MA (Di Giulio et al., 1978; Parsons & Justice, 1993). However, the studies performed by Huber et al. (2001a) and Laviola, Fiore, Loggi, and Alleva (1994) used males, and different dosing, age, and type of pain threshold testing. "
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ABSTRACT: The aim of the present study was to determine effects of methamphetamine (MA) exposure and cross-fostering on thermal nociceptive thresholds in different estrous phases in adult female rats. Rat mothers were exposed daily to injection of MA (5 mg/kg) or saline for 9 weeks: prior to impregnation, throughout gestation and lactation periods. Dams without any injections were used as an absolute control. On postnatal day 1, pups were cross-fostered so that each mother raised four pups of her own and eight pups from the mothers with the other two treatments. Offspring females were tested in adulthood (85-90 days) for thermal nociception as latency [s] of withdrawal reaction of forelimbs, hind limbs, and tail. Our results showed that prenatal MA exposure did not affect the nociception in adulthood, while postnatal MA exposure (i.e., MA administration to lactating mothers) had pro-nociceptive effects. The effect of postnatal MA exposure was apparent in both, fore- and hind limbs, while the latency to tail withdrawal reaction was the same among the groups. In addition, the pro-nociceptive effect of postnatal MA exposure did not depend on estrous cycle. This study indicates that postnatal but not prenatal exposure to MA affects nociception in adult female rats. However, it is still not clear whether the pro-nociceptive effect of postnatal MA exposure is linked to direct action of MA on neuronal organization, or to indirect action of MA mediated by impaired maternal care.
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ABSTRACT: The nigrostriatal and tuberoinfundibular-hypophyseal dopaminergic systems subserve different functions, the initiation of motor behaviors and the release of hormones from the pituitary, respectively. These differences are related to specific anatomical characteristics, the most important of which is the postsynaptic element. Although dopamine serves as the transmitter for both systems, the manner in which it reaches the receptive site in each system is fundamentally different. The nigrostriatal neurons form synaptic contacts with other neurons. Thus, the terminal and receptor are in close proximity. Dopamine released from the tuberoinfundibular system, on the other hand, must be transported the length of the infundibulum to reach the receptor, which is on a secretory cell rather than on a neuron. The postsynaptic element of the tuberohypophyseal system has not been as completely defined, although it may consist of neurosecretory cells. Not surprisingly, these systems, which are functionally and anatomically different, are regulated by different mechanisms.
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ABSTRACT: — Conjugated (sulphonyloxy) dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were synthesized from free DOPAC and HVA and used as reference compounds in their fluorimetric determination in rat brain (detection limit 0.2 nmol/g). The conjugated DOPAC and HVA form 29 and 36% of the total DOPAC and HVA found in rat striatum, respectively. Dopamine (DA) metabolism was studied in the rat striatum by following the decline of both free and conjugated DOPAC and HVA after treatment with pargyline (100mg/kg. i.p.) either alone or in combination with tropolone (100 mg/kg, i.p.). or from the accumulation of the free and conjugated acids after treatment with probenecid (100-500mg/kg. i.p.). The rates of decline were analysed by a non-linear curve fitting method using a simple model of DA metabolism that postulates the formation of the conjugates exclusively from the free acids, and HVA from DOPAC, with first order kinetics and single open compartments only. The curves computed all passed through the s.e.m. of every experimental point. The rate constants thus found indicate that DOPAC turnover is about 23nmol/g/h. Of this about 16 nmol/g/h are O-methylated to HVA, about 6 nmol/g/h are conjugated and less than 1 nmol/g/h is eliminated as free DOPAC. Of the HVA formed, about 8.5nmol/g/h are conjugated and about 7.5 nmol/g/h eliminated as free HVA. The conjugates accumulated after treatment with probenecid (1 h) faster than the free acids. The maximal accumulation of all four metabolites found (21 nmol/g/h) approximates the total turnover of DOPAC.
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