Biomedical subjects

Q Pei

Publications and source records attributed to Q Pei.

At least 19 recordsLinked to original sources

PubMed2004

Glutamate receptor activation is involved in 5-HT2 agonist-induced Arc gene expression in the rat cortex.

Brain 5-HT regulates the expression of gene transcription factor as well as novel effector immediate early genes (IEGs). The 5-HT regulation of the gene transcription factor IEG, c-fos, involves activation of 5-HT2A and ionotropic glutamate receptors. Here, we investigate whether these receptors are also involved in the regulation of the effector IEG, Arc. In rats, the 5-HT2 agonist DOI induced a marked increase in expression of Arc mRNA in a variety of cortical regions. This effect was blocked by the selective 5-HT2A receptor antagonist, MDL 100,907, but not the 5-HT(2B/2C) receptor antagonist, SB206553. The AMPA receptor antagonist GYKI 52466 also attenuated DOI-induced Arc mRNA expression, as did the NMDA receptor antagonist MK801 in some regions. Immunofluorescence studies showed that DOI increased Arc-immunoreactivity in cortical cells that expressed AMPA and NMDA receptor subunits but not the 5-HT2A receptor. Finally, DOI-induced Arc-immunoreactivity in cortical cells was extensively co-localised with c-fos-immunoreactivity. These results suggest that, as with c-fos expression, ionotropic glutamate receptors (AMPA and NMDA) are involved in 5-HT2A receptor-induced Arc expression. This finding, together with evidence of extensive Arc and c-fos co-localisation, suggests that 5-HT2A receptor activation may induce the expression of both effector and transcription factor IEGs via common molecular and cellular substrates.

Animals↗

PubMed2003

Bi-phasic change in BDNF gene expression following antidepressant drug treatment.

The gene for brain derived neurotrophic factor (BDNF) has recently received attention in relation to the therapeutic action of antidepressant treatment. This study aimed to clarify the influence of post drug interval on the effect of acute and repeated treatment with antidepressant drugs on BDNF gene expression in the rat brain. It was found that repeated administration of either the monoamine oxidase inhibitor tranylcypromine (TCP) or 5-hydroxytryptamine (5-HT) re-uptake inhibitors (fluoxetine, paroxetine and sertraline), evoke a bi-phasic and time-dependent effect on BDNF gene expression in the rat hippocampus (especially dentate gyrus). A down-regulation of the BDNF gene was detected at 4 h (TCP and fluoxetine) and an up-regulation at 24 h (TCP, paroxetine, fluoxetine, sertraline) after the last of twice daily injections for 14 days. After a single injection the down-regulation was detected at 4 h (TCP, fluoxetine, paroxetine and sertraline) but BDNF mRNA levels were not altered at 24 h post drug (TCP, fluoxetine and paroxetine). Administration of inhibitors of noradrenaline re-uptake (desipramine and maprotiline) or the atypical antidepressant mianserin had no effect on BDNF mRNA levels at either single (4 h post drug, desipramine) or repeated (24 h post drug, desipramine, maprotiline, mianserin) treatment. The gene expression for NT-3, which is distributed in a high density in the dentate gyrus, was not affected by single or repeated injections of antidepressant drugs (TCP, fluoxetine, paroxetine, sertraline, desipramine, maprotiline or mianserin) at 4 or 24 h post drug. In conclusion, these data show that the effect of antidepressant drugs on BDNF gene expression may be more complex and less widespread across treatments than previously thought. Thus, in this study drugs interacting with the central 5-HT system altered BDNF expression but the effect was bi-phasic over the 24 h post drug period.

Adrenergic Uptake Inhibitors↗

PubMed2003

Effect of different 5-HT1A receptor antagonists in combination with paroxetine on expression of the immediate-early gene Arc in rat brain.

Selective 5-HT(1A) receptor antagonists enhance the effect of selective serotonin reuptake inhibitors (SSRIs) on presynaptic 5-HT function, and have potential as antidepressant augmentation therapies. The present study tested the effect of different selective 5-HT(1A) receptor antagonists (WAY 100635, NAD-299, p-MPPI and LY 426965) in combination with a SSRI (paroxetine), on postsynaptic 5-HT function measured by increased expression of the immediate early gene, Arc. Paroxetine (5 mg/kg s.c.) combined with WAY 100635 (0.3 mg/kg s.c.) increased Arc mRNA in frontal, parietal and piriform cortices, and caudate putamen. Paroxetine (5 mg/kg s.c.) plus NAD-299 (1 or 5 mg/kg s.c.) had a similar effect. None of these drugs increased Arc mRNA when administered alone. Paroxetine (5 mg/kg s.c.) plus p-MPPI (8.5 mg/kg s.c.) also increased Arc mRNA but p-MPPI itself elevated Arc mRNA in many regions. Whilst LY 426965 (3 or 10 mg/kg s.c.) had no effect alone, when combined with paroxetine (5 mg/kg s.c.), the drug increased Arc mRNA in caudate putamen but not cortical regions.In conclusion, this study demonstrates that four 5-HT(1A) receptor antagonists augment the effect of an SSRI on Arc mRNA expression, which is suggestive of increased postsynaptic 5-HT function. However, the data reveal certain differences in the 5-HT(1A) receptor antagonists not recognised in models of presynaptic 5-HT function.

Aminopyridines↗

PubMed2003

Antidepressant drug treatment induces Arc gene expression in the rat brain.

The mechanism underlying the therapeutic effect of antidepressants is not known but neuroadaptive processes akin to long-term potentiation have been postulated. Arc (Activity-regulated, cytoskeletal-associated protein) is an effector immediate early gene implicated in LTP and other forms of neuroplasticity. Recent data show that Arc expression is regulated by brain 5-hydroxytryptamine neurones, a target of many antidepressants. Here in situ hybridisation and immunohistochemistry were used to examine whether Arc expression in rat brain is altered by antidepressant drug treatment. Repeated administration of the monoamine reuptake inhibitors paroxetine, venlafaxine or desipramine induced region-specific increases in Arc mRNA. These increases were greatest in regions of the cortex (frontal and parietal cortex) and hippocampus (CA1 layer) and absent in the caudate putamen. Repeated treatment with the monoamine oxidase inhibitor, tranylcypromine, increased Arc mRNA in a similar fashion to the monoamine reuptake inhibitors. The antidepressant drugs also increased the number of Arc-immunoreactive cells in the parietal cortex. Acute antidepressant injection, and repeated administration of the antipsychotic drug chlorpromazine, produced either limited or no changes in Arc mRNA. The data suggest that chronic treatment with antidepressant drugs induces Arc gene expression in specific regions across the rat forebrain. Up-regulation of Arc expression may be part of the process by which antidepressant drugs achieve long-term changes in synaptic function in the brain.

Animals↗

PubMed2001

Serotonergic cells of the rat raphe nuclei express mRNA of tyrosine kinase B (trkB), the high-affinity receptor for brain derived neurotrophic factor (BDNF).

Here we have studied the distribution of mRNA for tyrosine kinase B (trkB), the high-affinity receptor for brain-derived neurotrophic factor (BDNF) amongst serotonergic cell bodies of the raphe nuclei and their ascending projections into the dorsal hippocampus in the rat brain. Previous studies have shown that BDNF has got trophic action on serotonergic neurons. In the present study, we provide evidence that serotonergic neurons express mRNA for the functional receptor of BDNF, trkB. Intracerebro-ventricular (i.c.v.) injection of the 5-HT-specific neurotoxin, 5,7-dihydroxytryptamine, which lesions serotonergic cell bodies in the raphe nuclei as well as their ascending projections into the dorsal hippocampus, caused a dramatic loss of trkB mRNA from serotonergic cell bodies of the dorsal raphe nucleus. In contrast, there was no change in the abundance of trkB mRNA within the dorsal hippocampus. These findings provide direct evidence for the expression of trkB mRNA by serotonergic neurons and suggest distinct mechanisms of action of BDNF upon serotonergic neurons at the levels of their cell bodies and terminal projection sites.

5,7-Dihydroxytryptamine↗

PubMed2001

Electroconvulsive shock increases tachykinin NK(1) receptors, but not the encoding mRNA, in rat cortex.

Recent studies have suggested that the substance P (tachykinin NK(1)) receptor may be a pharmacological target for the treatment of mood disorders. Here, the effects of electroconvulsive shock on tachykinin NK(1) receptor gene expression in the rat brain was investigated. Rats received either a single electroconvulsive shock or five shocks on alternate days. Quantitative autoradiography with [(125)I]Bolton Hunter-substance P, and in situ hybridisation histochemistry, were used to measure tachykinin NK(1) receptor-binding site densities and mRNA abundance, respectively. Densities of tachykinin NK(1) receptor-binding sites were significantly increased in the cerebral cortex following repeated electroconvulsive shock compared to sham treated animals. Densities remained unchanged in the hippocampus, striatum and amygdala. Neither single nor repeated electroconvulsive shock altered tachykinin NK(1) receptor mRNA in the brain regions examined. Hence, repeated electroconvulsive shock increases tachykinin NK(1) receptors in the rat brain in a regionally specific way. Upregulation of receptor-binding sites without a change in mRNA indicates that translational or post-translational mechanisms underlie this process.

Amygdala↗

PubMed2001

Influence of thyroid hormone on 5-HT(1A) and 5-HT(2A) receptor-mediated regulation of hippocampal BDNF mRNA expression.

The aim of the present study was to determine the influence of thyroid hormone, T3, on the regulation of hippocampal BDNF expression by 5-HT receptor agonists. Chronic T3 administration prior to treatment with the 5-HT(1A) agonist, 8-OH-DPAT, significantly decreased BDNF mRNA in the dentate gyrus region of the hippocampus. Administration of 8-OH-DPAT did not alter hippocampal BDNF mRNA expression in naive, euthyroid rats. Pretreatment with the 5-HT(1A) antagonist, WAY 100635, completely blocked the 8-OH-DPAT-induced down-regulation of BDNF mRNA in chronic T3-treated rats. Acute T3 administration prior to 8-OH-DPAT treatment led to a small, but significant, decrease in hippocampal dentate gyrus BDNF mRNA. Acute or chronic administration of T3 did not alter the decrease in hippocampal BDNF mRNA induced by the 5-HT(2A/2C) receptor agonist, DOI. The influence of 8-OH-DPAT and DOI on hippocampal BDNF mRNA was also unaltered in rats rendered hypothyroid by propylthiouracil administration. Chronic T3 treatment or hypothyroidism did not influence the basal expression of hippocampal BDNF mRNA. The affinity and density of 5-HT(1A) receptors, and the hippocampal expression of 5-HT(1A) mRNA were also not influenced by chronic T3 treatment. The results of this study clearly demonstrate a powerful interaction between thyroid hormone and the 5-HT(1A) receptor in the regulation of hippocampal BDNF expression. Crosstalk between signal transduction cascades influenced by T3 and 5-HT(1A) receptors may mediate the synergistic effects of these systems on hippocampal BDNF expression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2000

High-speed electrically actuated elastomers with strain greater than 100%

Electrical actuators were made from films of dielectric elastomers (such as silicones) coated on both sides with compliant electrode material. When voltage was applied, the resulting electrostatic forces compressed the film in thickness and expanded it in area, producing strains up to 30 to 40%. It is now shown that prestraining the film further improves the performance of these devices. Actuated strains up to 117% were demonstrated with silicone elastomers, and up to 215% with acrylic elastomers using biaxially and uniaxially prestrained films. The strain, pressure, and response time of silicone exceeded those of natural muscle; specific energy densities greatly exceeded those of other field-actuated materials. Because the actuation mechanism is faster than in other high-strain electroactive polymers, this technology may be suitable for diverse applications.

Journal Article↗

PubMed2000

Serotonergic regulation of mRNA expression of Arc, an immediate early gene selectively localized at neuronal dendrites.

Arc (activity regulated, cytoskeleton associated protein) is an effector immediate early gene that is selectively localized in the neuronal dendrites. Elevation of brain 5-HT by the combined administration of the monoamine oxidase inhibitor, tranylcypromine (TCP, 5 mg/kg, i.p.), and the 5-HT precursor L-tryptophan (L-TP, 100 mg/kg, i.p.), increased Arc mRNA abundance in the cingulate, orbital, frontal and parietal cortices as well as in the striatum but a reduction was observed in the CA1 region of the hippocampus. The 5-HT releasing agent p-chloroamphetamine (PCA, 5 mg/kg, s.c.) also increased Arc mRNA in the cortical and striatal areas. Depleting brain 5-HT with the tryptophan hydroxylase inhibitor, p-chlorophenylalanine (pCPA, 300 mg/kg, i.p. for two days), on the other hand, significantly attenuated the increase in Arc mRNA induced by tranylcypromine and L-tryptophan (TCP/L-TP). Pretreatment with the 5-HT2 receptor antagonist ketanserin (2 mg/kg, i.p.) significantly attenuated the effect of TCP/L-TP in the cortex but only partially in striatum and did not affect the reduction in the CA1 region. The 5-HT2 agonist DOI (0.2, 1 and 2 mg/kg, i.p.) dose-dependently increased Arc mRNA abundance in cortical areas with a pattern similar to that of TCP/L-TP and PCA. DOI, however, had much weaker effects on Arc mRNA in the striatum and did not have any significant effect in the CA1, CA3 and the dentate gyms (DG) of the hippocampus. Pretreatment with ketanserin completely blocked the effect of DOI on Arc expression. These data suggest that Arc mRNA expression can be induced in the cortex by increases in extracellular 5-HT and that 5-HT2 receptors play a major part in mediating such effects. Additional 5-HT receptors as well as other neurotransmitters may also be involved, particularly in the striatum and in CA1 subfield of the hippocampus. Overall, our data suggest that expression of Arc mRNA is highly responsive to changes in brain 5-HT functions, and may provide a sensitive marker of postsynaptic 5-HT2(2A and 2C) receptor functions.

Animals↗

PubMed2000

Repeated electroconvulsive shock promotes the sprouting of serotonergic axons in the lesioned rat hippocampus.

This study reports the effect of repeated electroconvulsive shock on the sprouting of 5-hydroxytryptamine neurons in the partly lesioned rat dorsal hippocampus. We have adopted a 5-hydroxytryptamine homotypic collateral sprouting model to examine whether electroconvulsive shock administration altered the rate of 5-hydroxytryptamine axonal reinnervation of the dorsal hippocampus. The 5-hydroxytryptamine innervation of hippocampus originates from the median raphe via the cingulum bundle and the fimbria-fornix. Lesioning of the cingulum bundle has previously been shown to cause sprouting of intact 5-hydroxytryptamine afferents originating from the unharmed fimbria-fornix. Rats were unilaterally injected with the 5-hydroxytryptamine neurotoxin, 5,7-dihydroxytryptamine, into the right cingulum bundle and 5-hydroxytryptamine immunoreactivity in the dorsal hippocampus was investigated 1, 3, 6 and 12weeks after the injection. The lowest level of 5-hydroxytryptamine-immunoreactivity in the hippocampus was detected at three weeks after the lesion. At six weeks, 5-hydroxytryptamine immunoreactive fibres started to reappear, and at 12weeks the level of 5-hydroxytryptamine immunoreactivity was similar to that observed on the unlesioned side. Based on this time-course, six weeks was chosen as the time-point to investigate the action of a course of repeated electroconvulsive shock administrations. Repeated electroconvulsive shock (five shocks over 10days) doubled the number of sprouting 5-hydroxytryptamine-immunoreactive fibres and significantly increased levels of the 5-hydroxytryptamine metabolite, 5-hydroxyindoleacetic acid. The present data provide the first direct evidence that electroconvulsive shock enhances 5-hydroxytryptamine axon sprouting in the partly lesioned hippocampus. This is an effect which may contribute to the therapeutic effect of electroconvulsive therapy in major depression.

5,7-Dihydroxytryptamine↗

PubMed1999

Manipulations of brain 5-HT levels affect gene expression for BDNF in rat brain.

The aim of the present study was to investigate whether changes in brain 5-HT concentrations affect the expression of BDNF mRNA in rat brain. Brain 5-HT concentration in the rat was elevated by combined treatment with tranylcypromine and L-tryptophan, tranylcypromine alone, by a single dose of the 5-HT releasing agent p-chloroamphetamine (PCA) or by the selective 5-HT reuptake inhibitor paroxetine. 5-HT was depleted by either multiple p-chlorophenylalanine (pCPA) or PCA injections. The extent of 5-HT depletion following pCPA or PCA was monitored using 5-HT immunocytochemistry. BDNF mRNA abundance in treated rats and the corresponding vehicle injected control rats was studied by in situ hybridization histochemistry (ISHH). Two hours after the combined administration of tranylcypromine and L-tryptophan BDNF mRNA abundance in the dentate gyrus was significantly decreased but increased in the frontal cortex. Tranylcypromine alone or a single injection of PCA had similar effects on BDNF mRNA expression to the combination of tranylcypromine and L-tryptophan, i.e. they caused significant reductions of BDNF mRNA expression in dentate gyrus and increased it in frontal cortex. Paroxetine also reduced BDNF mRNA in DG but was without effect in frontal cortex. Multiple injections of both pCPA or PCA resulted in marked reductions of 5-HT immunoreactive axons in the hippocampus, pCPA being more effective. Both drugs significantly increased BDNF mRNA abundances in the dentate gyrus. Multiple PCA injections also increased BDNF mRNA expression in parietal cortex, while pCPA induced 5-HT depletion was ineffective. These results suggests that 5-HT modulates BDNF mRNA levels in rat brain.

Animals↗

PubMed1999

Alteration in expression of G-protein-activated inward rectifier K+-channel subunits GIRK1 and GIRK2 in the rat brain following electroconvulsive shock.

G-protein-activated inward rectifier potassium channels are coupled to a number of neurotransmitter receptors, including some monoamine receptors. In the present study we have investigated the effect of electroconvulsive shock on gene expression of the G-protein-activated inward rectifier potassium channel subunits G-protein-coupled inward rectifier K+-channel (GIRK1) and GIRK2 in the rat brain using in situ hybridization and immunocytochemistry. Acute electroconvulsive shock (a single shock) increased GIRK2 expression while causing a transient reduction of the messenger RNA abundance of GIRK1 in granule cells of the dentate gyrus. Chronic electroconvulsive shock (five shocks over 10 days) caused a larger increase in GIRK2 messenger RNA abundance, which was accompanied by an increase in GIRK2 immunoreactivity in the molecular layer of the dentate gyrus. Unlike for acute electroconvulsive shock, GIRK1 messenger RNA abundance in the dentate gyrus was significantly increased after chronic electroconvulsive shock. No significant alterations in GIRK1 and GIRK2 messenger RNA abundance were detected in the other brain regions studied, including the CA1 and CA3 subfields of the hippocampus, the frontal-parietal cortex and piriform cortex. The neuroanatomically specific changes in expression of the potassium channel subunits may directly influence neuronal excitability as well as the functions of G-protein-coupled neurotransmitter receptors.

Animals↗

PubMed1999

[Dynamic changes of nitric oxide and biochemistry in rats with intrahepatic cholestasis].

OBJECTIVE: To investigate the correlation between nitric oxide and biochemical changes of intrahepatic cholestasis. METHODS: Studies were made on endogenous NO, biochemical changes of cholestasis, liver mitochondrial function and renal excretion in a rat model at different time points after ANIT administration. RESULTS: In acute reactive phase, serum bilirubin, ALT, AKP, and bile acids significantly increased, accompanied by enhanced plasma NO and renal excretion. Liver NO increased and mitochondrial SDH activity decreased for 2-6 days after ANIT. There was a high negative correlation between liver NO and mitochondrial SDH activity (r = -0.92). CONCLUSION: These results show that higher liver NO may be an important mediator of intrahepatic cholestasis. However, plasma NO increase may play a role in rapidly decreasing serum bilirubin and restoring bile acids, ALT, and AKP to control levels by mediating enhanced renal excretion.

Alanine Transaminase↗

PubMed1998

Differential effects of electroconvulsive shock on the glutamate receptor mRNAs for NR2A, NR2B and mGluR5b.

We have studied the effects of single and repeated electroconvulsive shock (ECS) treatment on the mRNA levels of several glutamate receptors in the dentate gyrus and CA1 regions of the rat brain. In the dentate gyrus, such treatment elevated the mRNAs for the NMDA subunits NR2A and NR2B, but it reduced the mRNA for the metabotropic glutamate receptor mGlu5b. With the exception of NR2A, this effect was specific to the dentate gyrus. The changes in NR2B mRNA lasted the longest, but all changes had returned to control values after 48 h. The possible significance of such changes to the antidepressant effect of ECT is discussed.

Anatomy, Cross-Sectional↗

PubMed1998

Repeated electroconvulsive shock extends the duration of enhanced gene expression for BDNF in rat brain compared with a single administration.

Brain-derived neurotrophic factor (BDNF) is known to modulate synaptic function as well as to promote neuronal growth in the adult brain. The aim of the present study was to compare the duration of electroconvulsive shock (ECS)-induced BDNF gene expression following a single shock (acute ECS) to the more clinically relevant situation, where repeated shocks (chronic ECS) are administered. For this purpose, we have used quantitative in situ hybridisation with a 35S-labelled oligonucleotide probe complementary to mRNAs encoding genes for all forms of BDNF. The results confirm previous studies that the administration of ECS increases BDNF mRNA abundance in parts of rat brain with particularly marked changes in the granule cell layer of the dentate gyrus. We also for the first time show the long lasting nature of the increase in BDNF mRNA abundance measured after chronic ECS, i.e., significant increases in BDNF mRNA persisted up to 48 h after the last shock. Acute ECS at 6 h after the shock produced a slightly more pronounced effect on BDNF mRNA abundance than chronic ECS 6 h after the last shock. However, this change was not detectable already 24 h after a single ECS. These results indicate that repeated ECS induces adaptive changes in BDNF mRNA expression.

Animals↗

PubMed1998

Changes in mRNA abundance of microtubule-associated proteins in the rat brain following electroconvulsive shock.

Microtubule-associated proteins (MAPs) are involved in the maintenance of mature neuronal morphology, neurite outgrowth and neuronal plasticity. Alteration in MAP expression may underlie neuronal structural changes in response to seizure activity. The aim of the present study was to investigate whether electroconvulsive shock (ECS), an animal model of electroconvulsive therapy (ECT) in clinical treatment of depression, affected gene expression of MAPs in the rat brain. Using in situ hybridization, we studied the expression of encoding mRNA for MAPs in the brains of rats treated with ECS 5 times over 10 days. The abundance of mRNA encoding microtubule-associated protein 2 (MAP2), a dendritic MAP, was significantly increased (142% compared with controls) in the dentate gyrus 6 and 24 h after the last shock, and had returned to baseline levels within 48 h. These changes were confined to the dentate gyrus no significant changes were observed in CA1 and CA3 of the hippocampus. The increase in MAP2 expression was accompanied by an increase in MAP2 immunoreactivity in the molecular layer of the dentate gyrus. The abundance of mRNA encoding for tau, an axon-specific MAP, and MAP1B, an embryonic MAP, was unaffected by ECS. These data demonstrate that ECS specifically altered the mRNA and protein expression of MAP2 but had no effect on tau or MAP1B, and suggest that changes in MAP2 expression may be related to morphological changes in the dentate gyrus, particularly in the dendrites.

Animals↗

PubMed1998

Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat.

This study examined the effect of repeated treatment with the antidepressant drugs, fluoxetine, desipramine and tranylcypromine, on dopamine receptor expression (mRNA and binding site density) in sub-regions of the nucleus accumbens and striatum of the rat. The effect of these treatments on extracellular levels of dopamine in the nucleus accumbens was also measured. Experiments using in situ hybridisation showed that the antidepressants caused a region-specific increase in D2 mRNA, this effect being most prominent in the nucleus accumbens shell. In contrast, none of the treatments increased D1 mRNA in any of the regions examined. Measurement of D2-like binding by receptor autoradiography, using the ligand [3H]YM-09151-2, revealed that both fluoxetine and desipramine increased D2-like binding in the nucleus accumbens shell; fluoxetine had a similar effect in the nucleus accumbens core. Tranylcypromine, however, had no effect on D2-like binding in the nucleus accumbens but decreased binding in the striatum. In micro-dialysis experiments, our data showed that levels of extracellular dopamine in the nucleus accumbens were not altered in rats treated with either fluoxetine or desipramine, but increased by tranylcypromine. From our findings, we propose that the antidepressant drugs tested enhance dopamine function in the nucleus accumbens through either increased expression of post-synaptic D2 receptors (fluoxetine and desipramine) or increased dopamine release (tranylcypromine).

Animals↗

PubMed1997

Differential effects of acute and chronic electroconvulsive shock on the abundance of messenger RNAs for voltage-dependent potassium channel subunits in the rat brain.

The effect of acute and chronic electroconvulsive shock on the abundance of messenger RNAs encoding voltage-dependent potassium channel subunits in the rat brain was determined by in situ hybridization histochemistry with [35S]dATP-labelled oligonucleotides at 6 h, 24 h and three weeks following the last shock. The messenger RNA abundance of two voltage-dependent potassium channel subunits, Kv1.2 and Kv4.2, was altered by electroconvulsive shock but in different ways. In acute electroconvulsive shock experiments, Kv1.2 and Kv4.2 messenger RNA abundance in the dentate gyrus were reduced 6 h following the shock and returned to control levels after 24 h. In chronic electroconvulsive shock-treated rats, Kv1.2 messenger RNA abundance showed similar changes to those in acute electroconvulsive shock: it was reduced 6 h after the last shock and had recovered after 24 h. Kv4.2 messenger RNA abundance in chronic electroconvulsive shock-treated rats, however, showed adaptive changes: 6 h after the last shock there were no changes in its abundance while 24 h after the last shock there was a significant increase in the dentate gyrus. The changes in Kv1.2 and Kv4.2 messenger RNA abundance following electroconvulsive shock were only observed in the dentate gyrus and not in cornu ammonis 1 and cornu ammonis 3 of hippocampus or frontal-parietal cortex. Two other potassium channel subunits, Kv1.1 and Kv1.4, were not affected by either acute or chronic electroconvulsive shock. These findings indicate that acute and chronic electroconvulsive shock affect the gene expression of voltage-dependent potassium channel subunits with specificities for channel type, anatomical region and timing.

Animals↗