Neuroscience
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Comparative Study
Changes in peptidyl-prolyl cis/trans isomerase activity and FK506 binding protein expression following neuroprotection by FK506 in the ischemic rat brain.
FK506 is an immunosuppressant also showing neuroprotection following cerebral ischemia. FK506 binds to intracellular proteins (FKBP) which have a wide range of functions but have in common the peptidyl-prolyl cis/trans isomerase activity. Following transient focal ischemia, we have analyzed the expression of FKBP12, 52 and 65 and the total FKBP enzyme activity. ⋯ Cerebral ischemic damage to the brain was reduced by FK506. It was shown for the first time that neuroprotection by FK506 also included the suppression of the cerebral peptidyl-prolyl cis/trans isomerase activity of FKBP in vivo whereas the expression levels of FKBP12, 52 and 65 following ischemia changed slightly and FK506 treatment does not suppress the expression patterns. However, changes of FKBP enzymatic activity result in suppression of the stress cell body response in the peri-infarct area as observed by suppression of c-Jun phosphorylation and Fas-L expression.
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Comparative Study
Local mu and delta opioid receptors regulate amphetamine-induced behavior and neuropeptide mRNA in the striatum.
The purpose of this study was to investigate the role that mu and delta opioid receptor blockade has upon stimulant-induced behavior and neuropeptide gene expression in the striatum. Acute administration of amphetamine (2.5 mg/kg i.p.) caused an increase in behavioral activity and preprodynorphin, substance P, and preproenkephalin mRNA expression. Intrastriatal infusion of the mu opioid antagonist, H-D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH(2) (CTAP), or the delta opioid antagonist, H-Tyr-Tic[CH(2)NH]-Phe-Phe-OH (TIPPpsi), significantly decreased amphetamine-induced vertical activity. ⋯ However, preproenkephalin mRNA levels in the dorsal striatum were increased to the same extent by CTAP, amphetamine, or a combination of the two drugs. In contrast, TIPPpsi significantly decreased amphetamine-induced mRNA expression of all three neuropeptides. These data indicate that both mu and delta receptor subtypes differentially regulate amphetamine-induced behavior and neuropeptide gene expression in the rat striatum.
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Comparative Study
Repeated i.v. cocaine exposure produces long-lasting behavioral sensitization in pregnant adults, but behavioral tolerance in their offspring.
Repeated exposure to cocaine during sensitive periods of forebrain development produces specific, long-lasting changes in the structure and function of maturing neural circuits. Similar regimens of drug exposure in adult animals with mature, homeostatically regulated nervous systems produce neuroadaptations that appear to be quite different in nature and magnitude. We studied the ability of cocaine to induce behavioral sensitization and/or tolerance following repeated administration of i.v. cocaine (3 mg/kg, twice daily) to pregnant rabbits during the period of peak differentiation within the rabbit cerebral cortex (embryonic day [E] 16-E25). ⋯ The offspring, having received cocaine during the prenatal sensitive period, showed profound behavioral tolerance to the amphetamine challenge. In contrast, the mothers of these offspring, who received cocaine at the same dose and duration, and experienced the same period of withdrawal, exhibited robust behavioral sensitization. These data indicate that specific adaptive changes in neural signaling and/or circuitry that occur in response to repeated exposure to psychostimulants are highly dependent upon the maturational state of the brain during which the exposure occurs.
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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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Administration of typical and atypical antipsychotic drugs leads to activation of cells in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus, implicating important shared effects of these drugs. However, the exact cell types responding to antipsychotic drugs in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus are unclear. ⋯ The present study provides pharmacological evidence, at the cellular level in vivo, that the shared effects of antipsychotic drugs, whether typical and atypical, is activation of dynorphinergic GABA neurons in the nucleus accumbens shell, central amygdaloid nucleus, and midline thalamic central medial nucleus. Alternative ways to modulate dynorphinergic GABA neuronal activity or its target receptors might present an important new avenue for the treatment of schizophrenia and other psychotic disorders.