Neuroscience
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Comparative Study
Mechanisms underlying the inhibition of long-term potentiation by preconditioning stimulation in the hippocampus in vitro.
We have investigated the mechanisms underlying a form of metaplasticity, namely the inhibition by preconditioning stimulation of high frequency stimulation (HFS)-induced long-term potentiation (LTP) in the medial perforant path of the dentate gyrus. Preconditioning stimulation (weak 50 Hz) was found to inhibit subsequent LTP induction if applied 10-20 min, but not 2 or 45 min, prior to the HFS. Preconditioning stimulation in the form of low frequency stimulation did not block LTP induction. ⋯ The involvement of NMDAR in the preconditioning stimulation was shown by the ability of an NMDAR antagonist to prevent the inhibition of LTP by the preconditioning stimulation. The preconditioning inhibition of LTP induction was shown by the use of kinase inhibitors to involve activation of PKC and p38 MAP kinase, but not p42 MAP kinase or tyrosine kinase. We conclude that the preconditioning inhibition of LTP induction is a complex process which involves activation of NMDAR, group I and group II mGluR, and intracellular cascades activating PKC and p38 MAP kinase.
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Acute injection of morphine induces expression of the immediate-early genes c-Fos and JunB in several forebrain regions of the rat, in part through an N-methyl-D-aspartate (NMDA) receptor-dependent mechanism. Because membrane depolarization through (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors is believed to be necessary for full activation of NMDA receptors, we determined the role of AMPA receptors in morphine-induced c-Fos expression. Rats were given the AMPA receptor antagonist GYKI-52466 (12.9 mg/kg, i.p.) 15 min before morphine (10 mg/kg, s.c.), or the AMPA receptor enhancer CX516 (30 mg/kg, i.p.) 5 min after morphine. ⋯ To determine if activation of metabotropic glutamate receptors is involved in rapid effects of morphine on the brain, rats were given the type I metabotropic glutamate receptor antagonist (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA; 0.2 mg/kg, i.p.) or vehicle 30 min before morphine treatment. Pretreatment with AIDA completely blocked morphine-induced c-Fos expression in the caudate-putamen. Taken together, these results demonstrate involvement of both AMPA and type I metabotropic glutamate receptors in the acute effects of morphine on the forebrain, supporting an important role for glutamatergic neurotransmission mediated by non-NMDA glutamate receptors in morphine's actions.
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Comparative Study
Gonadal hormones differentially modulate cocaine-induced conditioned place preference in male and female rats.
There is accumulating evidence that suggests there are sex differences in behavioral and subjective responses to cocaine. However, it is not known whether differences in cocaine reward contribute to sex differences in these responses or whether gonadal hormones affect the rewarding properties of cocaine. In the present study, conditioned place preference (CPP), a measure of non-contingent reward, was used to determine the effects of endogenous gonadal hormones and of estrogen and progesterone replacement on cocaine reward. ⋯ While no effects of castration were observed, ovariectomy decreased levels of dopamine and serotonin in the ventral tegmental area. In females, progesterone replacement increased levels of serotonin and dopamine in the ventral tegmental area, while estrogen plus progesterone replacement increased dopamine levels in the nucleus accumbens. Collectively, these results indicate that ovarian hormones may influence cocaine reward by altering monoaminergic systems, which, in turn, may contribute to the current sex disparities in overall cocaine use.
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Serotonin antagonism in the lateral parabrachial nucleus (LPBN) enhances sodium appetite induced by hypovolaemia and angiotensin-mineralocorticoid activation, but produces no sodium intake in euhydrated animals. In the present work, male adult rats (n=21) that received bilateral injections of the serotonergic antagonist methysergide (4 microg/0.2 microl) into the LPBN combined to intragastric load of 2 M NaCl (2 ml/rat), ingested hypertonic NaCl (ingestion of 4.3 +/- 1.6 ml/2 h of 0.3 M NaCl versus vehicle into LPBN: 0.2 +/- 0.2 ml/2 h, P<0.05). ⋯ Ingestion of water (11.0 +/- 1.2 ml/2 h), and of 0.3 M NaCl (1.1 +/- 0.7 ml/2 h) were not altered by methysergide in NaCl loaded rats with misplaced LPBN injections (n=15). The ingestion of hypertonic NaCl by rats with serotonergic blockade in the LPBN suggests that the circuits subserving sodium appetite are activated, but at the same time strongly inhibited through the LPBN, during cell dehydration.
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Comparative Study
Constant light housing attenuates circadian rhythms of mPer2 mRNA and mPER2 protein expression in the suprachiasmatic nucleus of mice.
Constant light (LL) or constant dark (DD) environmental lighting conditions cause a free-running period and activity reduction in the rodent behavioral circadian rhythm. In order to understand the molecular process underlying behavioral rhythms in LL or DD housing conditions, we examined the circadian profile of mPer2 mRNA and mPER2 in the suprachiasmatic nucleus (SCN), a main oscillator, of free-running mice. The circadian expression rhythm of mPer2 in the SCN was dampened under 7-day LL conditions, whereas that of mPER2 protein was moderately attenuated and its expression peak delayed. ⋯ On the other hand, LL or DD housing did not affect the mPer2 gene and its product in the cerebral cortex. The present results suggest that mPER2 circadian expression in the SCN corresponds well with behavioral circadian oscillation under LL or DD conditions. Thus, the behavioral circadian rhythm seems to correlate with molecular clock works in the SCN.