Biomedical subjects

I K Ho

Publications and source records attributed to I K Ho.

At least 19 recordsLinked to original sources

PubMed2003

Changes in the brain kappa-opioid receptor levels of rats in withdrawal from physical dependence upon butorphanol.

Changes in kappa-opioid receptor levels have been implicated in the development of physical dependence upon and withdrawal from the mixed agonist-antagonist opioid, butorphanol. Immunoblotting analysis was performed to determine the levels of kappa- and mu-opioid receptors in brain regions of rats in withdrawal from dependence upon butorphanol or morphine. Physical dependence was induced by a 72 h i.c.v. infusion with either butorphanol or morphine (26 nmol/microl/h). Withdrawal was subsequently precipitated by i.c.v. challenge with naloxone (48 nmol/5 microl/rat), administered 2 h following cessation of butorphanol or morphine infusion. Immunoblotting analysis of kappa-opioid receptors from butorphanol-withdrawal rats showed significant increases in 11 of 21 brain regions examined, including the nucleus accumbens, amygdala, dorsomedial hypothalamus, hypothalamus, paraventricular thalamus, thalamus, presubiculum, and locus coeruleus, when compared with saline treated, non-dependent controls. In addition, significant reductions were found in the hippocampus and in cortical brain regions, including the parietal cortex and temporal cortex from butorphanol-withdrawal rats. These findings contrasted with those from morphine-withdrawal rats, in which the only changes noted were increases in the thalamus and paraventricular thalamus. Changes in the levels of the mu-opioid receptor protein were observed in 11 of 21 brain regions examined in morphine-withdrawal rats, but only in three of 21 in butorphanol-withdrawal rats. These results implicate a substantive and largely unique role for kappa-opioid receptors in mediation of the development of physical dependence upon, and the expression of withdrawal from, butorphanol, as opposed to the prototypical opioid analgesic, morphine.

Animals↗

PubMed2002

Focal kappa-opioid receptor-mediated dependence and withdrawal in the nucleus paragigantocellularis.

The nucleus paragigantocellularis (PGi) has been hypothesized to play an important role in the development of physical dependence on opioids, including the prototype mu-opioid receptor agonist, morphine, and the mixed agonist/antagonist, butorphanol, which shows selective kappa-opioid receptor agonist activity, in rats. In confirmation of previous work, electrical stimulation of the PGi in opioid-nai;ve rats induced stimulus-intensity-related, withdrawal-like behaviors similar to those observed during naloxone-precipitated withdrawal from dependence upon butorphanol. Novel findings were made in rats surgically implanted with cannulae aimed at the lateral ventricle and the right PGi and made physically dependent by intracerebroventricular infusion of either morphine (26 nmol/microl/h) or butorphanol (26 nmol/microl/h) through an osmotic minipump for 3 days. Two hours following termination of the opioid infusion, microinjections of naloxone (11 nmol/400 nl), a nonselective opioid receptor antagonist, or nor-binaltorphimine (nor-BNI) (3.84 nmol/400 nl), a selective kappa-opioid receptor antagonist, were made into the PGi of morphine-dependent and butorphanol-dependent rats. Discrete PGi injections precipitated withdrawal behaviors, with significant (P<.05) increases noted in the incidence of teeth chattering, wet-dog shakes, and scratching. Composite scores for behavioral withdrawal were significantly higher in nor-BNI-precipitated, butorphanol-dependent rats (score=6.8+/-0.6), in naloxone-precipitated, butorphanol-dependent rats (8.9+/-0.8), and in naloxone-precipitated, morphine-dependent rats (11.5+/-0.9) than in all other groups. Both kappa- and mu-opioid receptor mediated dependence can be demonstrated at the level of a discrete medullary site, the PGi, which further supports a specific role for this nucleus in elicitation of behavioral responses during opioid withdrawal.

Animals↗

PubMed2001

Lack of mu-opioid receptor leads to an increase in the NMDA receptor subunit mRNA expression and NMDA-induced convulsion.

The present study investigated in situ hybridization of N-methyl-D-aspartate (NMDA) receptor (NR) subunit mRNA and convulsion induced by intracerebroventricular injection of NMDA, in order to examine changes in NMDA receptor function in mu-opioid receptor gene knockout mice. Levels of NR1 and NR2A subunit mRNA were significantly increased in the parietal cortex (8.4 and 10.6%, respectively) and hypothalamus (8.7 and 15.2%, respectively) in mu-opioid receptor knockout mice. Levels of NR2B subunit mRNA were noted to be increased in the parietal cortex (9.1%), thalamus (7.7%), and hypothalamus (10.4%) in mu-opioid receptor knockout mice. The ED(50) for NMDA-induced convulsion in wild-type mice was 0.20 microg/10 microl/mouse. The ED(50) in mu-opioid receptor knockout mice was 0.14 microg/10 microl/mouse. There is a significant difference in the potency ratio of wild-type mice versus knockout mice (potency ratio: 1.44, P < 0.05). These results indicate that mu-opioid receptor knockout mice are more sensitive to NMDA-induced convulsion. Therefore, these results suggest that absence of mu-opioid receptor gene is accompanied by changes in the NMDA receptor system which can modulate the synaptic excitability in the process such as convulsion or epilepsy.

Animals↗

PubMed2001

Differential effects of morphine, DPDPE, and U-50488 on apomorphine-induced climbing behavior in mu-opioid receptor knockout mice.

The present study examined the hypothesis whether the opioid receptors (mu, delta, and kappa) contribute to a behavioral dopaminergic activation produced by dopamine receptor agonist, apomorphine, by comparing responses in wild type and mu-opioid receptor knockout mice. The data suggest that expression of mu-opioid receptors plays an important role in the enhancement of climbing behavior induced by apomorphine. Compared to wild type mice, a response in the dopaminergic behavior by treatment with delta-receptor agonist, DPDPE, is more sensitive to the mice lacking mu-opioid receptor. Treatment with kappa-receptor agonist, U-50488, is potentiated the apomorphine-induced climbing behavior in wild type and mu-opioid receptor knockout mice. These responses may be independent of that through mu-opioid receptors. Therefore, the our results show that dopaminergic activation measured by climbing behavior in mu-opioid receptors knockout mice are differently regulated by mu-, delta-, and kappa-opioid receptor agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2001

A quantitative histochemistry technique for measuring regional distribution of acetylcholinesterase in the brain using digital scanning densitometry.

Studies of brain acetylcholinesterase (AChE) are traditionally based on biochemical assays, immunoreactivity, and histochemistry. Conventional histochemistry yields rich morphological data from tissue sections but yields quantitative results only with great difficulty. Several histochemical methods developed in recent years, including microdensitometry, microphotometry, and video-based histochemistry, are effective in quantitative and detailed study of AChE in tissue sections. However, they are usually time-consuming. As we report here, we adapted digital scanning densitometry to quantitate AChE histochemical staining in brain sections. The AChE and butyrylcholinesterase (BuChE), as measured by the method, were heterogeneously distributed throughout the brain, results that are consistent with those obtained by biochemical methods. The staining intensity is dependent on section thickness, substrate concentration, and reaction time. The cholinesterase inhibitor methyl paraoxon significantly decreased AChE staining intensity. Furthermore, data acquired from densitometry are similar to those obtained by video-based microscopy or by spectrophotometry. The advantage of the densitometric measurements compared to other quantitative histochemical methods is that it is very rapid while collecting data that are equivalent in quality. Because the digital scanning densitometers provide high quality and sensitive imaging, wide dynamic ranges, and convenient image analysis software, they are very useful tools in quantitative histochemistry.

Acetylcholinesterase↗

PubMed2001

Uridine receptor: discovery and its involvement in sleep mechanism.

This review deals with the concept of sleep mechanism based on our uridine receptor theory. It is well established that uridine is one of the sleep-promoting substances, we have, therefore, synthesized new types of hypnotic compounds from oxopyrimidine nucleosides. Their mechanism of action in CNS depressant effects is elucidated based on the receptor theory. In this study, structure-activity relationship for CNS depressant properties, sleep-promoting effects, interaction with certain CNS receptors, and receptor binding assay of uridine derivatives as oxopyrimidine nucleoside were investigated. In the studies of structure-activity relationship of N3-substituted uridine, we found for the first time that both N3-benzyluridine and N3-phenacyluridine synthesized exhibited potent hypnotic activity (loss of righting reflex) by intracerebroventicular injection in mice. Moreover, certain derivatives of these compounds possessed synergistic effects with barbiturate and benzodiazepine, and decreased in spontaneous activity, motor incoordination, and antianxiety effects in mice. Especially, N3-phenacyluridine markedly enhanced pentobarbital- and diazepam-induced sleep by 6- and 70-fold, respectively. However, N3-benzyluracil and N3-phenacyluracil that have no ribose moiety did not possess any hypnotic activity, indicating specific effects of nucleoside derivatives. Effects of N3-benzyluridine on natural sleep in rats were thus examined. N3-Benzyluridine also possessed the sleep promoting effect assessed by electrocorticogram at the dose of 10 pmol. For elucidating the mechanism of action of N3-phenacyluridine, the interactions of this compound with benzodiazepine, GABA, 5-HT, or adenosine receptors were also investigated. Although the pharmacological activity of N3-phenacyluridine was high, the affinities to benzodiazepine, GABA, 5-HT, and adenosine receptors were quite low. [3H]N3-Phenacyluridine concentration-dependently bound to synaptic membrane prepared from the bovine brain. The Scatchard analysis revealed a single component of the binding site. This binding site is proposed here as a novel receptor called "uridine receptor" for hypnotic activity of the uridine derivatives. The rank order of the distribution of these specific binding sites was found to be striatum > thalamus > cerebral cortex > cerebellum > mid brain > medulla oblongata in the rat brain. In the metabolic study of N3-phenacyluridine, we found that this compound was exclusively metabolized to N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)- form, in mice. N3-(S)-(+)-alpha-Hydroxy-beta-phenylethyluridine possessed not only strong hypnotic activity but also a high affinity to the uridine receptor of synaptic membranes, while the (R)-isomer was low in both activities. Racemic mixture was shown to be intermediate for pharmacological effects of the compounds. These studies which used (R)- or (S)-isomer indicate that uridine binding site or uridine receptor, exists in the CNS and plays some role in sleep regulation in mammals as one of the triggering steps in inducing hypnotic activity. It is suggested that uridine is released from steps of nucleic acid-nucleic protein biosynthesis (catabolism), and reaches the binding sites in the areas of the brain which regulate natural sleep. The uridine dissociated from the receptor is then utilized for the synthesis of nucleic acid (anabolism). We propose here that the induction of sleep may be mediated by uridine through uridine receptor in the CNS, although the structure of uridine receptor is not yet elucidated.

Animals↗

PubMed2001

Region specific increase of dopamine receptor D1/D2 mRNA expression in the brain of mu-opioid receptor knockout mice.

Previous pharmacological studies have indicated the possible existence of functional interactions between opioidergic and dopaminergic neurons in the CNS. In this study, the expression of mRNAs encoding dopamine receptor D1/D2 was examined to investigate whether there is a change in the dopamine pathway of mice lacking the mu-opioid receptor by in situ hybridization technique. In the mu-opioid receptor knockout mice, the expression of dopamine receptor D1 mRNA was increased in the olfactory tubercle, nucleus accumbens, caudate putamen, and the layer VI of the neocortex compared with that of wild-type mice. The expression of dopamine receptor D2 mRNA was also increased in the olfactory tubercle, caudate putamen, and the nucleus accumbens of mu-opioid receptor knockout mice. These results indicate that there are compensational changes in the dopaminergic systems of mu-opioid receptor knockout mice.

Animals↗

PubMed2001

Effects of morphine on pentobarbital-induced responses in mu-opioid receptor knockout mice.

Effects of morphine on the potentiation of pentobarbital-induced responses were investigated using mu-opioid receptor knockout mice. The duration of loss of righting reflex, hypothermia, and loss of motor coordination induced by pentobarbital were measured after pretreatment with either morphine or saline. Morphine pretreatment failed to show potentiation of both pentobarbital-induced loss of righting reflex and hypothermia in mu-opioid receptor knockout mice, while it significantly potentiated these responses in the wild-type controls. For motor incoordination test, morphine potentiated pentobarbital-induced motor incoordination in the wild-type mice. However, morphine may have opposite effects in the mu-opioid receptor knockout mice. These results demonstrate that synergism between morphine and pentobarbital is not detected in mu-opioid receptor knockout mice and that potentiation of pentobarbital-induced loss of righting reflex and hypothermia by morphine is mediated through mu-opioid receptor. It was interesting to note that pentobarbital-induced decrease in body temperature was less severe in mu-opioid receptor knockout mice than in wild-type mice.

Animals↗

PubMed2001

Further evidence for a role of NMDA receptors in the locus coeruleus in the expression of withdrawal syndrome from opioids.

To examine a role of N-methyl-D-aspartate (NMDA) receptors in the locus coeruleus (LC) in the expression of the withdrawal signs from opioids, rats were continuously infused with morphine (a mu-opioid agonist, 26 nmol/microl per h) or butorphanol (a mu/delta/kappa-mixed opioid agonist, 26 nmol/microl per h) intracerebroventricularly (i.c.v.) through osmotic minipumps for 3 days. An LC injection of NMDA (0.1 and 1 nmol/5 microl) induced withdrawal signs in opioid-dependent animals. However, it did not precipitate any abnormal behaviors in saline-treated control rats. The expression of the withdrawal signs precipitated by NMDA (1 nmol/5 microl), glutamate (10 nmol/5 microl), or naloxone (an opioid antagonist, 24 nmol/5 microl) was completely blocked by pretreatment with a NMDA antagonist, MK-801 (5-methyl-10,11-dihydro-5H-dibenzo[a,d]cycloheptan-5,10-imine), 0.1 mg/kg, i.p. In animals that had been infused with opioids in the same manner, naloxone (48 nmol/5 microl, i.c.v.) precipitated withdrawal signs and increased extracellular glutamate levels in the LC of opioid-dependent rats measured by in vivo microdialysis method. Pretreatment with MK-801, however, did not affect the increases of glutamate levels in the LC. These results further demonstrate that the expression of opioid withdrawal induced by an expeditious release of glutamate in the LC region of opioid-dependent animals might be mainly mediated by the postsynaptic NMDA receptors.

Animals↗

PubMed2001

Modulation of the levels of NMDA receptor subunit mRNA and the bindings of [3H]MK-801 in rat brain by chronic infusion of subtoxic dose of MK-801.

The effects of continuous infusion of NMDA receptor antagonist MK-801 on the modulation of NMDA receptor subunits NR1, NR2A, NR2B, and NR2C were investigated by using in situ hybridization study. Differential assembly of NMDA receptor subunits determines their functional characteristics. Continuous intracerebroventricular (i.c.v.) infusion with MK-801 (1 pmol/10 microl/h) for 7 days resulted in significant modulations in the NR1, NR2A, and NR2B mRNA levels without producing stereotypic motor syndromes. The levels of NR1 mRNA were significantly increased (9-20%) in the cerebral cortex, striatum, septum, and CA1 of hippocampus in MK-801-infused rats. The levels of NR2A mRNA were significantly decreased (11-16%) in the CA3 and dentate gyrus of hippocampus in MK-801-infused rats. In contrast to NR2A, NR2B subunit mRNA levels were increased (10-14%) in the cerebral cortex, caudate putamen, and thalamus. However, no changes of NR2C subunits in cerebellar granule layer were observed. Using quantitative ligand autoradiography, the binding of NMDA receptor ligand [3H]MK-801 was increased (12-25%) significantly in almost all brain regions except in the thalamus and cerebellum after 7 days infusion with MK-801. These results suggest that region-specific changes of NMDA receptor subunit mRNA and [3H]MK-801 binding are involved in the MK-801-infused adult rats.

Animals↗

PubMed2001

MMPI-2 fake-bad scales: an attempted cross-validation of proposed cutting scores for outpatients.

Minnesota Multiphasic Personality Inventory-2 (MMPI-2) results were compared in 118 psychiatric outpatients given standard instructions, instructions to exaggerate their problems, instructions to feign a disorder they did not have, or instructions to feign global psychological disturbance. The groups were comparable on demographic, occupational and diagnostic characteristics as well as intake MMPI-2 results. Experimental MMPI-2 results showed that clinical scales were generally elevated in the feigning groups, with only modest differences across dissimulating instruction sets. The feigning groups had reliably higher scores than controls on all overreporting indexes examined, although no significant differences between feigning groups were present for overreporting indexes. Classification rates using previously proposed cutting scores for outpatients on individual feigning indexes showed near perfect specificity, but low to at best moderate sensitivity. Multiple regression analyses indicated that Gough's (1954) Dissimulation Scale (Ds2) was most strongly related to feigning status, and no other feigning scale contributed a significant increment in predictive power once Ds2 was entered.

Adult↗

PubMed2001

Possible existence of a novel receptor for uridine analogues in the central nervous system using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridines.

Uridine analogue binding sites, the so-called uridine receptor, were observed in the experiments on specific [3H]N3-phenacyluridine binding to bovine synaptic membranes using two isomers, N3-(S)-(+)- and N3-(R)-(-)-alpha-hydroxy-beta-phenethyluridine, as ligands. The potent hypnotic, N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine, but not the (R)-isomer, strongly inhibited [3H]N3-phenacyluridine binding. The racemate had inhibitory activity intermediate between that of the two alpha-hydroxy-beta-phenethyluridines ((R)- or (S)-isomers). The inhibitory constants of these compounds were determined. The Ki values of N3-phenacyluridine, alpha-hydroxy-beta-phenethyluridine (racemate), N3-(R)-(-)-, and N3-(S)-(+)-alpha-hydroxy-beta-phenethyluridine were 0.65, 397.4, 1908, and 10.2 nM, respectively. The present results indicate the existence of uridine receptors in the central nervous system in relation to their hypnotic activities reported previously.

Animals↗

PubMed2001

Hypnotic action of N3-substituted arabinofuranosyluracils on mice.

Methyl (2), ethyl (3), propyl (4), butyl (5), allyl (6), benzyl (7), o-, m-, p-xylyl (8-10), and alpha-phenylethyl (11) derivatives of arabinofuranosyluracil (1) were synthesized and their pharmacological effects in mice were examined by using hypnotic activity and synergism with pentobarbital as indices for the CNS depressant effects. At a dose of 2.0 micromol/mouse by intracerebroventricular injection, the values of mean sleeping time induced by 7-11 were 144, 154, 117, 33, and 34 min, respectively, whereas the alkyl (2-6) derivatives did not cause any hypnotic activity. N3-o-Xylylarabinofuranosyluracil (8) displayed the most potent hypnotic activity among the derivatives tested. Certain derivatives (6-11) significantly prolonged the pentobarbital-induced sleeping time compared to control. The present study indicated that substitution with benzyl and/or related groups on the N3-position of arabinofuranosyluracil produced CNS depressant effects.

Animals↗

PubMed2000

A protein kinase inhibitor, H-7, blocks naloxone-precipitated changes in dopamine and its metabolites in the brains of opioid-dependent rats.

The influence of an inhibitor of cAMP-dependent protein kinase and protein kinase C, H-7 [1-(5-isoquinolinesulfonyl)-2-methylpiperazine], on naloxone (an opioid receptor antagonist)-precipitated withdrawal signs and changes in levels of dopamine (DA) and its metabolites in morphine- or butorphanol-dependent rats was investigated. Animals were infused continuously with morphine (a mu-opioid receptor agonist) or butorphanol (a mu/delta/kappa mixed opioid receptor agonist) for 3 days. Naloxone precipitated withdrawal syndrome and decreased the levels of DA in the cortex, striatum, and midbrain; 3, 4-dihydroxyphenylacetic acid (DOPAC) in the cortex, striatum, limbic areas, and midbrain; and homovanilic acid (HVA) in the striatum, limbic areas, and midbrain regions. In animals rendered dependent on butorphanol, the results obtained were similar to those of morphine-dependent rats except for the changes in DOPAC levels. Concomitant infusion of H-7 and opioid blocked both the expression of withdrawal signs and the decreases in DA, DOPAC, and HVA levels in a dose-dependent manner. These results suggest that the enhancement of cAMP-dependent protein kinase and/or protein kinase C activity accompanying the increase of DA neuron activity during continuous infusion of opioids leads to an abrupt reduction in levels of DA and its metabolites precipitated by naloxone, which is intimately involved in the expression of physical dependence on opioids.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed2000

Comparison of G-protein activation in the brain by mu-, delta-, and kappa-opioid receptor agonists in mu-opioid receptor knockout mice.

Mice lacking the mu-opioid receptor gene have been developed by a gene knockout procedure. In this study, the activity of opioid receptor coupled G-proteins was examined to investigate whether there is a change in the extent of coupling for mu, delta-, and kappa-opioid receptors in mu-opioid receptor knockout mice. Selective agonists of mu- (DAMGO), delta- (DPDPE), and kappa- (U-69,593) opioid receptors stimulated [(35)S]GTPgammaS binding in the caudate putamen and cortex of wild-type mice. In contrast, only U-69,593 stimulated [(35)S]GTPgammaS binding in these regions of mu-opioid receptor knockout mice. These results confirmed the absence of G-protein activation by a mu-opioid receptor agonist in mu-opioid receptor knockout mice, and demonstrated that coupling of the kappa-opioid receptor to G-proteins is preserved in these mice. However, G-protein activation by the delta-opioid receptor agonist, DPDPE, was reduced in the mu-opioid receptor knockout mice, at least in the brain regions studied using autoradiography.

Alleles↗

PubMed2000

Involvement of mu-opioid receptors in potentiation of apomorphine-induced climbing behavior by morphine: studies using mu-opioid receptor gene knockout mice.

The present study examined the hypothesis that mu-opioid receptors contribute to a behavioral stimulation produced by stimulation of dopamine receptors by comparing responses in mu-opioid receptor knockout and wild type mice. Apomorphine-induced climbing behavior was augmented by 65%, in wild type mice, but not in mu-knockout, following subcutaneous administration of morphine (15 mg/kg). Moreover, pretreatment with either naloxone (an opioid receptor antagonist) or haloperidol (a mixed D(1)/D(2) receptor antagonist) eliminated the enhancement by morphine of climbing behavior in wild type mice. These results indicate that expression of mu-opioid receptors plays an important role in the enhancement of climbing behavior induced by the dopamine receptor agonist, apomorphine. Furthermore, this augmentation is mediated by interaction between dopamine and mu-opioid receptors.

Analgesics, Opioid↗

PubMed2000

kappa-opioid agonist stimulated regional distribution of [(35)S]GTPgammas binding in butorphanol continuously infused rat.

Butorphanol is a mixed agonist/antagonist opioid analgesic agent, which exerts its effects mainly by interaction with the kappa-opioid receptor. Opioid receptors are coupled to G proteins of G(i)/G(o) family, and recently a decrease in micro-opioid activation of G proteins has been reported in specific brainstem nuclei after chronic morphine administration. The influence of centrally administered butorphanol on agonist-stimulated G protein coupling was examined in the rat brain, using in situ guanylyl-5'-O-(gamma-[(35)S]thio)-triphosphate (GTPgammaS) binding autoradiography. Rats were treated with butorphanol (26 nmol/microl/h) by intracerebroventricular infusion via osmotic minipumps for 3 days. The distribution of [(35)S]GTPgammaS binding in the brain 7 h after the termination of butorphanol infusion was measured in the presence or absence of the selective kappa-opioid agonist, U-50,488. This agonist significantly increased [(35)S]GTPgammaS binding in the parietal cortex, caudate putamen, thalamus, and central gray of control rats, but not in those regions of the butorphanol-infused animals. These results suggest that chronic administration of butorphanol developed tolerance and abolished U-50,488 activation of G proteins in these brain areas.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2000

N-Methyl-D-aspartate receptor NR1 subunit mRNA level was decreased in rat brain during pentobarbital withdrawal.

We examined the effect of continuous intracerebroventricular (i.c.v. ) administration of pentobarbital on the level of N-Methyl-D-aspartate receptor NR1 subunit mRNAs in different regions of rat brain by in situ hybridization histochemistry. Animals were rendered tolerant to pentobarbital by continuous i.c.v. infusion (300 microgram/10 microliter/h for 6 days) through pre-implanted cannulae connected to osmotic mini-pumps, and dependent, by abrupt withdrawal from pentobarbital. NR1 subunit mRNA level was significantly decreased in the entorhinal cortex, cingulate, caudate-putamen, septum, and the CA1 of hippocampus in pentobarbital withdrawal rats. The level of NR1 mRNAs was decreased in only CA1 of hippocampus in pentobarbital tolerant rats. These results indicate that withdrawal from i.c.v. infusion with pentobarbital decreases in NR1 subunit expression in the rat brain, suggesting that changes in expression of NR1 subunit may contribute to the development of withdrawal from pentobarbital.

Animals↗