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M C Boadle-Biber

Publications and source records attributed to M C Boadle-Biber.

At least 19 recordsLinked to original sources
PubMed2001

Further studies on the activation of rat median raphe serotonergic neurons by inescapable sound stress.

Previous studies, using a biochemical measure of serotonergic neuronal function, show that inescapable, randomly presented sound pulses activate serotonergic neurons in the rat median raphe but not dorsal raphe nucleus. The present study reveals that this activation also occurs in serotonin projection areas, in hippocampus, nucleus accumbens and cortex but not in caudate nucleus. The selectivity of this response is examined by comparing the response to sound stress with that produced by morphine, a treatment known to selectively activate dorsal raphe but not median raphe serotonergic neurons. Two approaches are used in Sprague-Dawley rat to measure the activation of serotonergic neurons: (1) determination ex vivo of accumulation of 5-hydroxytryptophan (5-HTP) in tissue from the dorsal and median raphe nuclei, hippocampus, cortex, caudate nucleus, and nucleus accumbens following in vivo inhibition of aromatic amino acid decarboxylase; and (2) measurement of extracellular serotonin levels in hippocampus, caudate nucleus, and nucleus accumbens. Sound stress increases 5-HTP accumulation in median raphe nucleus, hippocampus, cortex, and nucleus accumbens, but not dorsal raphe nucleus or caudate nucleus. Sound stress also enhances extracellular serotonin levels in hippocampus and nucleus accumbens, but not caudate nucleus. In contrast, the morphine treatment enhances 5-HTP accumulation in dorsal raphe nucleus, cortex and caudate nucleus, but not in median raphe nucleus, hippocampus or nucleus accumbens. Furthermore, it increases extracellular serotonin levels in only the caudate nucleus. The combined effects of sound stress and morphine on 5-HTP accumulation are identical to those obtained by each treatment individually. These findings provide further support for the presence of serotonergic neurons within the median raphe nucleus that have a unique response profile. These neurons may have an important role in responses or adaptations to stress.

Adaptation, Physiological↗
PubMed1996

Neurotensin inhibits the activation of midbrain serotonergic neurons produced by random inescapable sound.

Previous studies indicate that exposure of rats to randomly presented, inescapable loud sound, referred to as sound stress, increases central serotonin turnover as well as the ex vivo activity of tryptophan hydroxylase (EC 1.14.16.4), the rate-limiting enzyme in serotonin biosynthesis. The purpose of this investigation was to determine whether intracerebroventricular (i.c.v.) administration of neurotensin (NT), a tridecapeptide found within the midbrain raphe, influences the activation of the midbrain serotonergic neurons by sound stress. Accumulation of 5-hydroxytryptophan (5-HTP) in vivo, in the presence of the aromatic amino acid decarboxylase inhibitor, NSD 1015 (m-hydroxybenzylhydrazine, 100 mg/kg i.p.) given immediately before a 30 min sound stress, was used as an index of in vivo tryptophan hydroxylase activity. Sound-stressed rats had significantly higher levels of 5-HTP in cortex and midbrain compared to sham-stressed controls. NT (0.01-3.3 nmol total), given i.c.v., 5 min prior to 30 min sound stress, completely blocked the enhanced accumulation of 5-HTP, but had no effect on basal accumulation of 5-HTP, except at the highest doses of 1.0 or 3.3 nmol, which others have previously shown to inhibit basal serotonergic metabolism. NT (0.3 and 3.3 nmol) blocked the increase in cortical tryptophan hydroxylase activity, ex vivo, in response to 30 min sound stress, without affecting basal enzyme activity. These and other recent data suggest a possible role for endogenous NT in the regulation of serotonergic neuronal activity within the midbrain raphe.

5-Hydroxytryptophan↗
PubMed1995

Differential activation of the 5-hydroxytryptamine-containing neurons of the midbrain raphe of the rat in response to randomly presented inescapable sound.

Estimates of 5-hydroxytryptamine (5-HT) turnover in response to 30 min of inescapable, randomly presented, loud sound (sound stress) were obtained for regions of rat brain containing 5-HT perikarya by means of 5-hydroxytryptophan (5-HTP) accumulation after administration of an inhibitor of aromatic amino acid decarboxylase (100 mg/kg i.p., m-hydroxybenzylhydrazine, NSD 1015). Sound stress increased 5-HTP accumulation in the median raphe nucleus (MRN) twofold over that from sham-stressed controls, but did not change 5-HTP accumulation significantly in dorsal raphe nucleus (DRN) or hindbrain. These findings indicate that the 5-HT perikarya of the MRN but not those of the DRN or hindbrain are activated by sound stress, thus, provide further evidence for a functional distinction between the 5-HT neurons of these two midbrain nuclei.

5-Hydroxytryptophan↗
PubMed1994

Sound stress activation of tryptophan hydroxylase blocked by hypophysectomy and intracranial RU 38486.

The rapidly reversible increase in cortical or midbrain tryptophan hydroxylase activity observed ex vivo after exposure of rats to 1-h sound stress was blocked by hypophysectomy, but not sham hypophysectomy, and restored by dexamethasone administration to the hypophysectomized animals (500 micrograms/day i.p. for 3 days). The response to sound stress was also lost with deafferentation of the hypothalamus. These results indicate that hypothalamic control of adrenal glucocorticoids is required for the serotonergic response to sound stress. The glucocorticoid antagonist, RU 38486, given intracerebroventricularly (200 micrograms/day for 4-5 days) or bilaterally, into the region of the central nucleus of the amygdala (100 micrograms 15 min before stress), blocked the sound stress-induced increase in tryptophan hydroxylase activity. In contrast, the antimineralocorticoid, RU 26752, was without effect. The block obtained with RU 38486 suggests that glucocorticoid is required by the neurons that relay the effects of sound stress to the rostrally projecting serotonergic neurons.

Acoustic Stimulation↗
PubMed1994

Intracranial dehydroepiandrosterone blocks the activation of tryptophan hydroxylase in response to acute sound stress.

Bilateral infusion of dehydroepiandrosterone (DHEA) given intracerebroventricularly blocked the sound stress-induced increase in tryptophan hydroxylase activity observed ex vivo in midbrain and cortex but had no effect on the level of tryptophan hydroxylase activity from sham-stressed rats. DHEA (20 micrograms total dose) given bilaterally into the region of the central nucleus of the amygdala, 30 min prior to 1 h sound stress, also blocked the increase in enzyme activity in a dose-dependent manner. The DHEA treatment did not alter the activation of the enzyme seen in vitro in the presence of phosphorylating conditions. The effect of DHEA was steroid specific in that other sex steroids, such as estrogen, androgens, or progesterone, were without any effect. Coadministration, 20 micrograms each, of the potent glucocorticoid agonist, RU 28362, with DHEA 30 min prior to 1 h sound stress completely blocked the DHEA suppressive effect on sound stress-induced increases in tryptophan hydroxylase activity. The results obtained suggest that DHEA blocks this increase in tryptophan hydroxylase activity by antagonizing the effects of glucocorticoid.

Acoustic Stimulation↗
PubMed1993

Evidence that corticotropin-releasing factor within the extended amygdala mediates the activation of tryptophan hydroxylase produced by sound stress in the rat.

Non-endocrine corticotropin-releasing factor (CRF) is believed to be involved in mediating stress behaviors in rats. The present study investigated the role of CRF in mediating the activation of tryptophan hydroxylase, the rate-limiting enzyme in serotonin synthesis, produced in response to sound stress. Bilateral injections of 0.5-3.0 micrograms of CRF directed towards the central nucleus of the amygdala increased tryptophan hydroxylase activity measured ex vivo when compared to vehicle-injected controls. This increase in enzyme activity, like that due to sound stress, was reversed in vitro by alkaline phosphatase. Intra-amygdala CRF (0.5 microgram) also enhanced the in vivo accumulation of 5-hydroxytryptophan (5-HTP) following the administration of m-hydroxylbenzylamine (NSD-1015, 200 mg/kg). The activation of tryptophan hydroxylase, produced by intra-amygdala CRF, was blocked by the CRF receptor antagonist alpha-helical CRF9-41 (10 micrograms). Additionally, the 5-HT1A agonist, gepirone, given either systemically (10 mg/kg) or intracerebrally into the region of the dorsal raphe (14 micrograms), blocked the tryptophan hydroxylase response to CRF. CRF did not increase tissue levels of 5-hydroxyindole acetic acid (5-HIAA) or the ratio of 5-HIAA to serotonin (5-HT) within the striatum of the same animals in which tryptophan hydroxylase activity was quantified, an effect produced by sound stress. Thus, while intra-amygdala CRF failed to mimic the sound stress response in its entirety, these data suggest that CRF is involved in mediating the activation of tryptophan hydroxylase produced by sound stress within the midbrain serotonin neurons.

Acoustic Stimulation↗
PubMed1992

Effect of gepirone on increases in tryptophan hydroxylase in response to sound stress.

Pretreatment (15 min) of male rats with gepirone given parenterally (10 mg/kg i.p.) or intracranially into the dorsal raphe nucleus (14 or 21 micrograms) blocks the rapidly reversible increase in brain tryptophan hydroxylase activity and 5-hydroxyindolamine acetic acid tissue levels seen in vitro after 1-h acute sound stress. Chronic gepirone treatment over 28 days (40 mg/day s.c.) prevents the stable enzyme activity increase induced by repeated sessions of sound stress, and the rapidly reversible increase always observed following sound stress. The gepirone metabolite, 1-(2-pyrimidinyl)-1-piperazine, is inactive in each of these experiments. Transient blood pressure elevations occur with each sound presentation, but no persistent hypertension is observed with repeated sound-stress exposures. Gepirone may block the sound stress-induced biochemical increases by its inhibition of serotonergic neuronal firing in the dorsal raphe nucleus that is mediated by its agonist action at the somatodendritic (5-HT1A) autoreceptors.

Animals↗
PubMed1992

Increase in cortical and midbrain tryptophan hydroxylase activity by intracerebroventricular administration of corticotropin releasing factor: block by adrenalectomy, by RU 38486 and by bilateral lesions to the central nucleus of the amygdala.

Corticotropin releasing factor (CRF) infused bilaterally into the lateral ventricles of awake, chronically cannulated, male Sprague-Dawley rats produced a dose-dependent increase in the in vitro activity of cortical and midbrain tryptophan hydroxylase after 60 min. The maximal increase in enzyme activity of 60% over that of vehicle-treated controls was reached 45 min after an infusion of 3 micrograms CRF. The increase in enzyme activity after a single dose of CRF resembled that seen after exposure of rats to an acute sound stress: it was reversed by preincubation of the enzyme preparation with alkaline phosphatase and was nonadditive with the increase in activity obtained in the presence of phosphorylating conditions. The response to intracerebroventricularly administered CRF was abolished by bilateral adrenalectomy, but restored by repeated daily systemic administration of the synthetic glucocorticoid, dexamethasone (500 micrograms/day, i.p. for 3 days), to the adrenalectomized rats. Intracerebroventricular administration of the glucocorticoid antagonist, RU 38486 (200 micrograms/day for 4 days), also blocked the acute increase in tryptophan hydroxylase activity in response to CRF. Finally, bilateral lesions to the central nucleus of the amygdala, a region involved in mediating behavioral, endocrine and autonomic responses to stressful stimuli, abolished the increase in enzyme activity in response to intraventricular CRF. The glucocorticoid sensitivity of the response to CRF, as well as the involvement of the central nucleus of the amygdala support the view that CRF may have a role in mediating the enhancement of tryptophan hydroxylase activity by acute sound stress.

Adrenalectomy↗
PubMed1990

The increases in rat cortical and midbrain tryptophan hydroxylase activity in response to acute or repeated sound stress are blocked by bilateral lesions to the central nucleus of the amygdala.

Sound stress (SS) (120-dB pulses of 100 ms duration, every min for 1 h) produces an elevation of in vitro cortical or midbrain tryptophan hydroxylase activity from male Sprague-Dawley rats that is abolished, in vitro, by incubation of the enzyme preparation with alkaline phosphatase. SS, when repeated on 3 different occasions, the first 2 sessions 24 h apart and the 2nd and 3rd session separated by 48 h, produces a stable increase in the in vitro enzyme activity that is unaffected by alkaline phosphatase. Bilateral lesions to the central nucleus of the amygdala block both increases in enzyme activity obtained in response to acute and repeated SS, but leave enzyme activity from sham-stressed rats unaffected.

Amygdala↗
PubMed1990

Increases in the activity of tryptophan hydroxylase from rat cortex and midbrain in response to acute or repeated sound stress are blocked by adrenalectomy and restored by dexamethasone treatment.

Exposure of male Sprague-Dawley rats to acute sound stress (2 s, 110 dB sound pulses presented randomly every minute for 1 h) increases the in vitro activity of cortical and midbrain tryptophan hydroxylase by an alkaline phosphatase-reversible mechanism. Repeated exposure to sound stress on three separate days produces a stable increase in enzyme activity that persists 24 h after the termination of the stress and is insensitive to alkaline phosphatase. Adrenalectomy abolishes both increases in enzyme activity to acute or repeated sound stress but does not change baseline levels of enzyme activity. The synthetic glucocorticoid, dexamethasone, (500 micrograms/day i.p.) given for 3 days or 5 out of 6 days, starting day 3 after adrenalectomy, restores the increases in enzyme activity in adrenalectomized rats exposed, respectively, to acute or repeated sound stress. The mineralocorticoid, aldosterone (5 micrograms/day s.c.), does not substitute for dexamethasone in acutely sound-stressed, adrenalectomized rats. Dexamethasone does not alter control levels of enzyme activity in either adrenalectomized rats or rats with intact adrenals (sham-adrenalectomized), but is required to allow the increase in enzyme activity in response to acute or repeated sound stress to be expressed. The effect of the glucocorticoid, thus, appears to be a permissive one.

Acoustic Stimulation↗
PubMed1989

Blockade of morphine-induced increases in brain tryptophan hydroxylase activity by systemic pretreatment with CCK-8: no reversal by vagotomy.

The treatment of rats with CCK-8 suppresses the behavioral responses to subsequent injection of opiates. We have investigated the possibility that peripherally administered CCK-8 can also suppress a neurochemical response to opiates, namely the increase in brain tryptophan hydroxylase (TrpH) activity and tissue 5-hydroxyindole acetic acid (5-HIAA) which results from morphine administration. While morphine sulfate (4 mg/kg s.c.) roughly doubled brain TrpH activity and tissue 5-HIAA 40 min after injection, pretreatment with CCK-8 (5 micrograms/kg i.p., 10 min prior to morphine) completely abolished this neurochemical change induced by morphine. Doses of CCK-8 as low as 1 microgram/kg were effective in blunting the morphine-induced increase in cortical TrpH activity, but the desulfated form was ineffective at doses of 5 and 100 micrograms/kg. Subdiaphragmatic vagotomy did not prevent the effect of CCK-8.

Animals↗
PubMed1989

Increase in the activity of tryptophan hydroxylase from cortex and midbrain of male Fischer 344 rats in response to acute or repeated sound stress.

Exposure of male Fischer 344 rats to an acute sound stress consisting of 100 dB tones of 2-s duration presented at random 60-s intervals for 2 h, increased cortical and midbrain tryptophan hydroxylase activity, measured in vitro, 50% over that from sham-stressed animals. This increase in enzyme activity was observed when animals were killed immediately, but not 1 h, after termination of the sound stress. It was non-additive with the increase in activity induced by incubation of enzyme under phosphorylating conditions and could be reversed in vitro with alkaline phosphatase. Graded increases in enzyme activity were obtained with increments of sound intensity (90-120 dB). In contrast to acute stress, chronic sound stress (110 dB) repeated over a period of 1, 2 or 6 weeks (3 sessions per week each of 2-h duration) produced a 50% increase in cortical enzyme activity that persisted 24 h after the termination of the stress and was not reversed by alkaline phosphatase. However, a further increase in enzyme activity could be produced if the chronically stressed animals were exposed to an acute 2-h stress (110 dB) immediately before being killed. This additional increase in activity was reversible in vitro by alkaline phosphatase and non-additive with that produced by incubation under phosphorylating conditions. In summary, acute sound stress produced a prompt, reversible activation of tryptophan hydroxylase. Repeated exposure to sound stress induced a persistent increase in enzyme activity that was detected 24 h after the last stress.

Acoustic Stimulation↗
PubMed1987

Activation of cortical tryptophan hydroxylase by acute morphine treatment: blockade by 6-hydroxydopamine.

Acute morphine produced a dose-dependent, naloxone-sensitive, reversible increase in tryptophan hydroxylase activity in low speed supernatants of midbrain, pons-medulla and cerebral cortex but not spinal cord. The increase in cortical enzyme activity was blocked by 6-hydroxydopamine pretreatment, could be reversed in vitro by incubation with alkaline phosphatase and was non-additive with the increase in enzyme activity induced in the presence of phosphorylating conditions. Morphine administration produced an increase in Vmax but no change in Km of cortical enzyme for substrate, tryptophan, or the artificial reduced pterin cofactor, 6-methyl-5,6,7,8-tetrahydropterin. The failure of morphine to increase spinal tryptophan hydroxylase activity despite enhancement of enzyme activity in medulla indicates regional differences in responsiveness of the enzyme to in vivo activation.

Alkaline Phosphatase↗
PubMed1986

AGN 2979 [3(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4, 4-dimethylpiperidine-2,6-dione]. An inhibitor of the activation of tryptophan hydroxylase.

AGN 2979 [3-(3-methoxyphenyl)-3-(3-dimethylaminopropyl)-4, 4-dimethylpiperidine-2,6-dione] blocked the increase in tryptophan hydroxylase activity that occurred when slices of brainstem were exposed to a depolarizing medium or to agents that mobilize intracellular pools of calcium, but it had no effect on the activity of enzyme prepared from slices of brainstem incubated in control medium. AGN 2979 also blocked the calcium-calmodulin-dependent activation of tryptophan hydroxylase that was seen when supernatant preparations of the enzyme were exposed to phosphorylating conditions but not the activation induced by calcium-dependent proteases that was triggered by millimolar calcium concentrations. An identical pattern of inhibition has been found with the antipsychotic drugs, haloperidol and fluphenazine [Boadle-Biber, Biochem. Pharmac. 31, 2495 (1982)]. The sensitivity to the same inhibitors of both the activation of tryptophan hydroxylase produced by pretreatment of brainstem slices and that induced by incubation of supernatant preparations of enzyme under phosphorylating conditions suggests involvement of a common mechanism of enzyme activation in response to these different treatments.

Animals↗
PubMed1985

Effect of clonidine on the activity of tryptophan hydroxylase from rat brainstem following in vivo or in vitro treatment.

In vivo administration of clonidine hydrochloride (Catapres) via tail vein injection produced a rapid increase in brainstem tryptophan hydroxylase activity assayed in vitro under subsaturating conditions of reduced pterin cofactor, 6MPH4. Enzyme activity returned to and remained at control levels about 60 min after treatment with low doses of clonidine (5 micrograms/kg). However, with higher doses of the drug (15 micrograms/kg), enzyme activity fell to below control levels for about an hour. Incubation of brainstem slices with clonidine also produced a dose-dependent increase in enzyme activity. The increase in enzyme activity appears to be mediated indirectly since it was abolished when brain catecholamine levels were depleted by pretreatment with 6-hydroxydopamine 8 days prior to clonidine treatment. The kinetic properties of tryptophan hydroxylase prepared 25 and 90 min after clonidine administration indicate that the initial increase and subsequent decrease in enzyme activity seen under these conditions may be due to changes in apparent Vmax of the enzyme.

Animals↗