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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 2 of 2. This is the beginning of the thread.
Posted by JohnX2 on March 28, 2002, at 16:50:53
Impact of metyrapone on MK-801-induced alterations in the rat dopamine D1 receptors.
Czyrak A, Mackowiak M, Fijal K, Chocyk A, Wedzony K.
Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.
Our earlier studies have shown that changes in serum corticosterone levels played an important role in the acquisition of sensitization to MK-801, a non-competitive NMDA receptor antagonist. Dopaminergic mechanisms are found to be particularly important in the development of sensitization; hence in the present study we assessed the binding of [3H]SCH 23390 at brain dopaminergic D1 receptors, after administration of MK-801 (0.4 mg/kg), in rats in which corticosterone synthesis was inhibited by metyrapone (150 + 50 mg/kg). Such metyrapone pretreatment prevented the increases in serum corticosterone level induced by MK-801. The binding studies, using receptor autoradiography, were performed in the following brain structures: the striatum, nucleus accumbens, olfactory tubercle and substantia nigra. Metyrapone per se did not change or slightly increased D1 receptor binding in the substantia nigra, while in other brain structures tested it decreased the number of these receptors by about 30%. MK-801 increased the level of D1 receptors in the nucleus accumbens core and olfactory tubercle, being without effect in the remaining brain structures tested. In rats which were pretreated with metyrapone, the effect of MK-801 on D1 receptors was inhibited in the nucleus accumbens core only. In substantia nigra, metyrapone provoked the MK-801-induced decrease in D1 receptors whereas in all other structures MK-801 reversed the effects of metyrapone on D1 receptors. Additionally, the effect of metyrapone and MK-801 on grooming behavior induced by D1 receptor agonist SKF 38393 (10 mg/kg) was tested. Metyrapone did not influence grooming induced by SKF 38393, but significantly potentiated the inhibitory effect of MK-801 on this behavior. Finally, we found that metyrapone did not influence the expression of the sensitization induced by MK-801. Our results seem not to support hypothesis that MK-801 evokes enhancement of dopaminergic neurotransmission (at the level of D1 receptors) via corticosterone liberation, since in most brain regions studied inhibition of increases in corticosterone level did not prevent MK-801-induced effects on D1 receptors. The present study may suggest that NMDA receptors are involved in the corticosterone-dependent regulation of the density of the D1 receptors.
PMID: 9566029 [PubMed - indexed for MEDLINE]
Posted by JohnX2 on March 28, 2002, at 17:02:38
In reply to d1receptors, mk-801, corticosterone, posted by JohnX2 on March 28, 2002, at 16:50:53
1: Neuroscience 1999;88(3):837-45 Related Articles, Books, LinkOut
Effects of corticosterone on excitatory amino acid responses in dopamine-sensitive neurons in the ventral tegmental area.Cho K, Little HJ.
Psychology Department, Durham University, UK.
The ventral tegmental area is involved in reward processes and in drug dependence and sends dopaminergic projections to the nucleus accumbens and prefrontal cortex. Stress, and glucocorticoid hormones, are thought to play an important role in the development of drug dependence, but there has been little investigation of the effects of these hormones on ventral tegmental function. The present study examined the effects of corticosterone on single-unit recordings from dopamine-sensitive neurons in the ventral tegmental area in midbrain slices. At concentrations of 100 nM and above, corticosterone potentiated the responses to N-methyl-D-aspartate. This effect was not seen when the calcium concentration of the bathing medium was reduced to 0.1 mM. Responses to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) and kainic acid were also considerably potentiated, at concentrations of corticosterone over 100 nM, while there was some evidence of decreases in these responses at the 100 nM concentration of this hormone. Aldosterone, at concentrations of 100 nM and above reduced the responses to N-methyl-D-aspartate, but had no effects at lower concentrations. RU38486, which acts as an antagonist at glucocorticoid (Type II) receptors, prevented the effects of corticosterone on responses to N-methyl-D-aspartate, with no effect on the spontaneous firing rate or on the effects of N-methyl-D-aspartate in the absence of corticosterone. The latter result, and the effects of aldosterone, suggest that the potentiation of responses to N-methyl-D-aspartate was mediated through Type II glucocorticoid receptors. This study suggests that potentiation of responses to excitatory amino acids by corticosterone may alter the function of ventral tegmental neurons during stress, and it is possible that this effect is involved in the development of drug dependence.
PMID: 10363821 [PubMed - indexed for MEDLINE]
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