Biomedical subjects

K J Renner

Publications and source records attributed to K J Renner.

At least 19 recordsLinked to original sources

PubMed2006

Corticotropin-releasing factor in the dorsal raphe elicits temporally distinct serotonergic responses in the limbic system in relation to fear behavior.

The neurotransmitters serotonin and corticotrophin-releasing factor are thought to play an important role in fear and anxiety behaviors. This study aimed to determine the relationship between corticotrophin-releasing factor-evoked changes in serotonin levels within discrete regions of the limbic system and the expression of fear behavior in rats. The effects of corticotrophin-releasing factor administration to the serotonin cell body regions of the dorsal raphe nucleus on fear behavior, behavioral activity, and extracellular serotonin levels were assessed in freely moving rats with microdialysis probes implanted into the central nucleus of the amygdala and the medial prefrontal cortex. Infusion of corticotrophin-releasing factor (0.5 microg) into the dorsal raphe rapidly induced freezing behavior, which was positively correlated with an immediate increase in serotonin release in the central nucleus of the amygdala. In contrast, cessation of freezing behavior correlated with a delayed and prolonged increase in serotonin release within the medial prefrontal cortex. Our findings suggest that corticotrophin-releasing factor-induced freezing behavior is associated with regionally and temporally distinct serotonergic responses in the limbic system that may reflect differing roles for these regions in the expression of fear/anxiety behavior.

Analysis of Variance↗

PubMed2003

Monoaminergic activity in subregions of raphé nuclei elicited by prior stress and the neuropeptide corticotropin-releasing factor.

Corticotropin-releasing factor (CRF) coordinates neuroendocrine responses to stressful stimuli; one mechanism through which CRF may modulate hypothalamic-pituitary-adrenal axis activity is via actions on neuromodulatory systems such as serotonergic systems. Recent electrophysiological studies and the distribution of CRF receptors within midbrain and pontine raphé nuclei suggest that stress and CRF may have actions on topographically organized subpopulations of serotonergic neurones. We compared the effects of vehicle or intracerebroventricular r/hCRF injections (0, 0.1, 1 or 10 micro g) in rats previously maintained in home cages or restrained for 1 h, 24 h before injection, on monoamine and monoamine metabolite tissue concentrations in the dorsal (lateral wings, rostral midline, caudal midline), median (rostral, caudal) and interfascicular raphé subdivisions of the midbrain and pontine raphé nuclei, using brain microdissection and high-performance liquid chromatography with electrochemical detection. At the lowest dose studied (0.1 micro g), CRF infusions in previously stressed rats decreased 5-hydroxytryptophan (5-HTP) and 5-hydroxyindoleacetic acid (5-HIAA) concentrations only within the rostral median raphé nucleus. At higher doses, CRF infusions in previously stressed rats increased tissue concentrations of 5-HTP, serotonin (5-HT), or the serotonin metabolite, 5-HIAA, within rostral (but not caudal) regions of the median and dorsal raphé nuclei. By contrast, restraint stress alone had no effect on tissue concentrations of 5-HTP, 5-HT or 5-HIAA measured 24 h later in any subdivision, while CRF injections in rats not previously exposed to restraint stress, with few exceptions, also had no effect. These results suggest that the effects of CRF on serotonergic function are context-dependent, dose-dependent, and regionally specific within subdivisions of the brainstem raphé nuclei.

5-Hydroxytryptophan↗

PubMed2001

Rapid changes in monoamine levels following administration of corticotropin-releasing factor or corticosterone are localized in the dorsomedial hypothalamus.

Monoaminergic systems are important modulators of the neuroendocrine, autonomic, and behavioral responses to stress-related stimuli. The male roughskin newt (Taricha granulosa) was used as a model system to investigate the effects of corticotropin-releasing factor (CRF) or corticosterone administration on tissue concentrations of norepinephrine, epinephrine, dopamine, 3,4-dihydroxyphenylacetic acid, serotonin, and 5-hydroxyindoleacetic acid (5-HIAA) in microdissected brain areas. Intracerebroventricular infusion of 25 or 50 ng of CRF increased locomotor activity and site-specifically increased dopamine concentrations within the dorsomedial hypothalamus 30 min after treatment when compared to vehicle-treated controls. In further studies, male newts were treated as follows: (1) no injection, no handling, (2) saline injection, or (3) 10 microg corticosterone and then placed in a novel environment. Monoamine and monoamine metabolite concentrations were similar in the unhandled and saline-injected controls 20 min after treatment. In contrast, corticosterone-injected newts had elevated concentrations of dopamine, serotonin, and 5-HIAA in the dorsomedial hypothalamus (a region that contains dopamine- and serotonin-accumulating neuronal cell bodies in representatives of all vertebrate classes) but not in several other regions studied. These site-specific neurochemical effects parallel neurochemical changes observed in the dorsomedial hypothalamic nucleus of mammals following exposure to a variety of physical and psychological stress-related stimuli. Therefore, these changes may reflect highly conserved, site-specific neurochemical responses to stress and stress-related neurochemicals in vertebrates. Given the important role of the dorsomedial hypothalamus in neuroendocrine, autonomic, and behavioral responses to stress, and a proposed role for this region in fast-feedback effects of glucocorticoids on the hypothalamo-pituitary-adrenal axis, these stress-related monoaminergic changes are likely to have important physiological or behavioral consequences.

Animals↗

PubMed2001

The role of monoaminergic nuclei during aggression and sympathetic social signaling.

A social sign stimulus that is sympathetically induced affects aggressive approaches and influences serotonergic, dopaminergic and noradrenergic activity in the brainstem nuclei of Anolis carolinensis. Darkening of postorbital skin via sympathetic activation of adrenal catecholamines and beta(2)-adrenergic receptors provides a visual signal that forms more rapidly in dominant than subordinate males during social interactions. This signal limits aggressive interactions. Males were painted postorbitally with green or black paint and then exposed to a mirror. Aggressive approaches to the mirror were inhibited in males viewing a reflection with darkened eyespots, and increased in males viewing a reflection without eyespots (hidden). Noradrenergic turnover in the raphe and locus ceruleus were greatest in test subjects that viewed a reflection with eyespots hidden by green paint. Perception of darkened eyespots stimulated greater serotonergic turnover in raphe, locus ceruleus and substantia nigra/ventral tegmental area (SN/VTA). Dopaminergic turnover was higher in the raphe and SN/VTA of Anolis that viewed a reflection with darkened eyespots. However, these animals had lower dopamine turnover in the locus ceruleus than isolated and hidden eyespot groups. Of the possible roles of perikarya on central function and behavior, our results suggest feedback, cross-nuclear regulation, and some independence of function between nuclei and the forebrain terminal fields. Decreased serotonergic activity corresponds with increased aggression only in the raphe, suggesting that the raphe nuclei might be important for this behavioral trait. Increased serotonergic, noradrenergic and dopaminergic activities in SN/VTA in Anolis that view a reflected opponent with dark eyespots suggests that the SN/VTA might be directly involved in recognition of this social sign stimulus and the resulting inhibition of aggression.

Aggression↗

PubMed2000

Treadmill exercise training augments brain norepinephrine response to familiar and novel stress.

In a test of hypothalamic-pituitary-adrenal (HPA) cortical and hypothalamic-pituitary-gonadal (HPG) interaction during familiar and novel stress, we previously reported that treadmill exercise training led to blunted plasma adrenocorticotrophin (ACTH) response to acute treadmill running but a hyper-responsiveness of ACTH after novel immobilization. In this follow-up analysis, we examined whether those results might be plausibly explained by a similar effect of treadmill exercise training on increased levels of norepinephrine (NE) in hypothalamic and limbic brain regions which synergize to modulate the release of ACTH during stress. Ovariectomized Sprague-Dawley rats that had been exercise trained by treadmill running or remained sedentary for 6 weeks received intramuscular injections of estradiol benzoate (Eb) or sesame oil on each of 3 days prior to 15 min of familiar treadmill running or novel immobilization. Treadmill exercise training, regardless of Eb treatment or type of stress, increased NE levels in the paraventricular (PVN), arcuate, medial preoptic, and ventromedial areas of the hypothalamus and protected against depletion of NE in the locus coeruleus, amygdala, and hippocampus. We conclude that treadmill exercise training has a hyperadrenergic effect in brain areas that modulate hypothalamic regulation of ACTH release during stress that is independent of HPA-HPG interaction and novelty of the stressor. To help elucidate these findings, the effects of treadmill exercise training on A1-A2 nuclei which innervate the PVN and their relationship with the limbic and hypothalamic responses we report require study.

Amygdala↗

PubMed2000

Stress induces rapid changes in serotonergic activity: restraint and exertion.

Rapid activation of central serotonergic systems occurs in response to the social stress of aggression in dominant lizards. The most rapid expression of serotonergic activity occurs in nucleus accumbens, hippocampus and brainstem. To compare previously measured responses induced by social stressors with those provoked by physical stress, serotonergic activity was examined following restraint stress (handling) and forced physical exertion. After handling, some male Anolis carolinensis were placed on a race track and either run until there was no movement following 1 min of prodding, or half that time. Controls were killed without treatment. Lizards stressed by handling showed rapid (25 s) increases in serotonergic activity (5-HIAA/5-HT) in striatum, dorsal cortex, locus ceruleus, and nucleus accumbens. Other changes in serotonergic systems caused by stress occurred in raphe and hippocampus. Serotonergic changes induced by handling stress were reversed by exercise (to 50% maximal exertion time) in subiculum, striatum and nucleus accumbens. The serotonergic profile of lizards run until they would no longer respond to prodding (maximal exertion time) was significantly different from that for more acute exertion in hippocampus, subiculum, striatum, medial amygdala, locus ceruleus, area postrema, and raphe. Physical stress (handling) mimicked social stress by producing rapid serotonergic changes in hippocampus, subiculum, nucleus accumbens and locus ceruleus. In contrast, the medial amygdala, which has previously been demonstrated to respond serotonergically to social stress only after a temporal delay, did not show a rapid response to restraint stress.

Animals↗

PubMed2000

Serotonergic responses to corticosterone and testosterone in the limbic system.

Glucocorticoids secreted peripherally during stressful events act on central monoaminergic systems. In particular, serotonergic mediation of social behavior, such as aggression and reproduction, may be affected by glucocorticoids. This study was undertaken to determine if systemically administered corticosterone would rapidly affect central monoaminergic activity. Male Anolis carolinensis (N = 8 each group) were injected intraperitoneally with 10 or 100 micrograms corticosterone, 10 micrograms testosterone, or saline. Twenty minutes after treatment, brains were rapidly dissected and frozen and then microdissected (punch diameter 300 microm) and analyzed by high-performance liquid chromatography. Serotonergic turnover (estimated by 5-hydroxyindoleacetic acid/serotonin) in the hippocampus and medial amygdala was significantly enhanced by systemic corticosterone. Both of these regions of the brain have been associated with social stress. Testosterone also enhanced turnover in the hippocampus. The effect of corticosterone and testosterone may be to modulate socially induced differences in serotonergic response. Rapid, but short-lived, glucocorticoid stimulation of serotonin release suggests a possible mechanism for mediation of changing social behavioral events.

Amygdala↗

PubMed1999

Brain noradrenergic responses to footshock after chronic activity-wheel running.

Effects of physical activity on brain noradrenergic response to footshock were examined. Male Fischer 344 rats were randomly assigned to shoebox cages with (AW) or without (SED) 24-hr access to an activity wheel for 4-5 weeks. Extracellular levels of norepinephrine (NE) and 3,4-dihydroxyphenyl-acetic acid (DOPAC) in the brain frontal cortex were measured in 20-min samples of microdialysate taken during a 2-hr baseline, 40 min of scrambled footshock, and a 1-hr recovery. Levels of messenger RNA (mRNA) for tyrosine hydroxylase (TH), c-fos, and prepro-galanin in the locus coeruleus were measured by in situ hybridization histochemistry with autoradiographic analysis. NE levels were the same for SED and AW rats at baseline but were elevated in SED compared with AW during and after footshock. Levels of mRNA for TH and c-fos were elevated after footshock but did not differ between SED and AW. Our findings suggest that wheel running blunts NE release in the brain frontal cortex in response to footshock but does not influence expression of the gene that encodes TH in the locus coeruleus.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1999

GABAergic regulation of lordosis: influence of gonadal hormones on turnover of GABA and interaction of GABA with 5-HT.

The role of GABAergic neurons in activating female sexual behavior and possible mechanisms for GABAergic effects on behavior were examined in female rats. First, effects of the ovarian hormones estrogen and progesterone (P), at doses which promote lordosis, on levels and turnover/activity of GABA, were examined in brain areas which regulate lordosis. Utilizing AOAA, an inhibitor of GABA degradation, the accumulation rate of GABA (turnover/activity) was assessed in ovariectomized (Ovx), Ovx + estrogen and Ovx + estrogen + P-treated rats. Estradiol increased GABA accumulation rates in the arcuate-median eminence and in the area dorsal to and surrounding the VMN (VMN-S). P administration following estrogen priming enhanced GABA turnover in the medial preoptic area (mPOA) and further increased turnover in the VMN-S while GABA turnover decreased in the dorsomedial nucleus. No effects of hormones were noted in the VMN itself or in the dorsal midbrain central gray. Reverse dialysis of the GABAA antagonist bicuculline into the basomedial hypothalamus was associated with a time-dependent inhibition of lordosis and a 300% increase in 5-HT release in the basomedial hypothalamus as measured by in vivo dialysis. These results provide additional evidence that GABAergic neurons mediate the physiological regulation of female sexual behavior and suggest that such mediation may involve an interaction with 5-HT containing neurons.

Animals↗

PubMed1998

Regional and temporal separation of serotonergic activity mediating social stress.

Stressful aggressive interaction stimulates central serotonergic activation in telencephalon as well as brainstem. Social roles can be distinguished by monoamine activity following aggression. Pairs of male lizards, Anolis carolinensis, were allowed to fight and form dominant/subordinate relationships. In micropunched regions of telencephalon, the greatest serotonergic changes occur in subordinate males. In hippocampal cortex and nucleus accumbens, subordinate males have increased 5-hydroxyindoleacetic acid/serotonin at 1 h following the fight. In these areas the ratio gradually decreases over a week of cohabitation, as was previously reported for brainstem. Medial and lateral amygdala develop increased serotonergic activity more slowly, with the greatest increase being evident following a week of interaction. Turnover, serotonin and 5-hydroxyindoleacetic acid levels in amygdala escalate over the first week of interaction in subordinate males, and return to baseline by one month. In dominant males, the pattern is accelerated, with the most extensive serotonin system activity present at 1 h, then decreasing over a month. The patterns of serotonergic activation are so similar in hippocampus, nucleus accumbens and brainstem that a co-ordinated response may be involved in mediating short-term social stress and aggression. Similarly, medial and lateral amygdala exhibit corresponding, but delayed patterns in subordinate males, suggesting a co-ordinated response in these regions mediating longer-term stress responses. These data are consistent with rapid neuroendocrine stress modulation in dominant individuals, and delayed serotonergic activity changes in subordinate males.

Aggression↗

PubMed1997

Activity wheel running reduces escape latency and alters brain monoamine levels after footshock.

We examined the effects of chronic activity wheel running on brain monoamines and latency to escape foot shock after prior exposure to uncontrollable, inescapable foot shock. Individually housed young (approximately 50 day) female Sprague-Dawley rats were randomly assigned to standard cages (sedentary) or cages with activity wheels. After 9-12 weeks, animals were matched in pairs on body mass. Activity wheel animals were also matched on running distance. An animal from each matched pair was randomly assigned to controllable or uncontrollable inescapable foot shock followed the next day by a foot shock escape test in a shuttle box. Brain concentrations of norepinephrine (NE), dopamine (DA), dihydroxyphenylacetic acid (DOPAC), 5-hydroxytryptamine (5-HT), and 5-hydroxyindole acetic acid (5-HIAA) were assayed in the locus coeruleus (LC), dorsal raphe (DR), central amygdala (AC), hippocampus (CA1), arcuate nucleus, paraventricular nucleus (PVN), and midbrain central gray. After prior exposure to uncontrollable foot shock, escape latency was reduced by 34% for wheel runners compared with sedentary controls. The shortened escape latency for wheel runners was associated with 61% higher NE concentrations in LC and 44% higher NE concentrations in DR compared with sedentary controls. Sedentary controls, compared with wheel runners, had 31% higher 5-HIAA concentrations in CA1 and 30% higher 5-HIAA concentrations in AC after uncontrollable foot shock and had 28% higher 5-HT and 33% higher 5-HIAA concentrations in AC averaged across both foot shock conditions. There were no group differences in monoamines in the central gray or in plasma prolactin or ACTH concentrations, despite 52% higher DA concentrations in the arcuate nucleus after uncontrollable foot shock and 50% higher DOPAC/DA and 17% higher 5-HIAA/5-HT concentrations in the PVN averaged across both foot shock conditions for sedentary compared with activity wheel animals. The present results extend understanding of the escape-deficit by indicating an attenuating role for circadian physical activity. The altered monoamine levels suggest brain regions for more direct probes of neural activity after wheel running and foot shock.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1996

In vivo evidence for progesterone dependent decreases in serotonin release in the hypothalamus and midbrain central grey: relation to the induction of lordosis.

The effects of progesterone (P) on serotonin (5HT) overflow in the ventromedial hypothalamus (VMH), preoptic area (POA) and midbrain central grey (MCG) were studied using in vivo microdialysis. Ovariectomized rats, pretreated with 5 micrograms estradiol, were anesthetized with chloral hydrate and stereotaxically implanted with dialysis probes directed towards one of the respective brain sites. Extracellular 5HT levels stabilized 3 to 5 h following probe implantation. Under stable baseline conditions, perfusion of 1 microM tetrodotoxin through the dialysis probe resulted in 60-65% reduction in 5HT overflow in the brain areas studied. In experiments testing the effect of P on 5HT overflow, rats were subcutaneously injected with 0.5 mg P or propylene glycol vehicle. Samples were analyzed for 5HT at 20 min intervals for 4 h after treatment. Perfusate levels of 5HT were not significantly changed in the VMH, POA or MCG in vehicle-treated rats. Similarly, P treatment failed to significantly alter 5HT overflow in the POA. In the VMH, perfusate levels of 5HT were significantly reduced 60 min after P treatment. Decreases in perfusate 5HT levels were detected 20 min after P in the MCG. The decreases in 5HT overflow measured in the VMH and MCG following P treatment persisted for the remainder of the sampling period with the exception of 1 time point in the VMH. The results provide in vivo evidence for P-influenced decreases in 5HT release in the VMH and MCG. The rapid decrease in extracellular 5HT in the MCG suggests that this effect may represent a non-genomic action of P. These results are discussed in relation to the role of 5HT in the regulation of lordosis behavior.

Animals↗

PubMed1996

Catecholamines and indoleamines in the central nervous system of a urodele amphibian: a microdissection study with emphasis on the distribution of epinephrine.

Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected, and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection. The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluidcontacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines. The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines.

Animals↗

PubMed1993

Pargyline-induced increase in serotonin levels: correlation with inhibition of lordosis in rats.

The effect of intrahypothalamic infusion of the monoamine oxidase inhibitor pargyline on lordosis behavior and monamine levels in the preoptic area and hypothalamus was examined. Progesterone-facilitated lordosis was blocked by pargyline in half the treated rats. The inhibition of lordosis was correlated with increases in serotonin and dopamine levels in the ventromedial nucleus of the hypothalamus and serotonin levels in the arcuate nucleus-median eminence when compared to controls or pargyline-treated rats with high levels of lordosis responding. Changes in norepinephrine levels were not correlated with changes in behavior. The results provide further evidence for an inhibitory role of basomedial hypothalamic serotonin in the control of female sexual behavior.

Animals↗

PubMed1993

Effect of progesterone on serotonin turnover in rats primed with estrogen implants into the ventromedial hypothalamus.

The effect of progesterone (P) on serotonin (5-HT) turnover was studied in nine brain regions in ovariectomized rats primed with bilateral intracerebral implants of estradiol benzoate (1:250 cholesterol) directed towards the ventromedial hypothalamus (VMN). Two days after surgery, animals received P (0.5 mg SC), and were pretested for lordosis behavior. After a 44-h recovery period, rats with LQ > or = 60 were randomly divided into groups that received either a second behavior test or IP injections of saline or pargyline (4 h after P or V). P treatment decreased pargyline-induced accumulation of 5-HT in the VMN (pars lateralis), the lateral midbrain central grey (IMCG), and the periventricular region (PVE, anterior hypothalamic region). The 5-HIAA/5-HT ratios were significantly decreased in the VMN and PVE in P-treated animals. These results support the hypothesis that P-influenced decreases in serotonergic activity in the VMN contribute to the facilitation of female receptivity, and also suggest that steroid-mediated actions in the VMN may lead to changes in serotonergic activity in the IMCG and PVE.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Cholecystokinin antagonists inhibit in vivo voltammetric signals generated by KCl-induced slow wave depolarization in rat caudate.

The effect of sulfated cholecystokinin octapeptide (CCK-8S) on the generation of slow wave depolarisation in the rat caudate-putamen (CPu) was studied using in vivo voltammetry. Pressure-ejection of 50 microM CCK-8S into the CPu induced voltammetric signals recorded at widely spaced Nafion-coated carbon fiber microelectrodes. Based on the in vitro selectivity properties of the electrodes, the signals were predominantly due to increases in extracellular concentrations of dopamine (DA). The similar propagation rates of the signals induced by CCK-8S and 100 mM KCl suggests that the CCK-8S-induced signals represent a slow wave depolarization (SWD). Since the CPu was refractory to a second CCK-8S stimulus, the effects of CCK antagonists on DA signals associated with 100 mM KCl-induced SWD were evaluated. Proglumide (4-64 mg/kg) and lorglumide (20-640 micrograms/kg), administered intravenously, decreased KCl-induced DA signals in the CPu in a dose-dependent manner. The antagonistic effect of lorglumide on the KCl-induced signals was partly reversed 130 min after drug administration. The generation of a SWD by CCK-8S and the inhibitory effects of CCK-8S antagonists on KCl-induced signals suggest that the susceptibility of the CPu to KCl-induced SWD may be enhanced by CCK-8S.

Animals↗

PubMed1992

In vivo voltammetric evidence for the detection of norepinephrine release in the thalamus of freely moving rats.

The ventrobasal complex (VB) of the thalamus was monitored in awake rats for the presence of norepinephrine (NE) overflow following pharmacological manipulations and physiological stimulation. Overflow was detected using chronoamperometry with electrochemically pretreated, Nafion-coated carbon fiber microelectrodes. In vivo evaluation of the electrode responses to systemic drug administration showed that alpha-methyl-p-tyrosine (alpha-MPT) and FLA-63 caused decreases in baseline current. Increases in baseline current in the VB were observed in animals treated with pargyline, yohimbine and yohimbine injected 2 h postpargyline. The results suggest that an electrochemical signal primarily due to NE overflow can be monitored in thalamic regions. Vigorous somatosensory stimulation induced small, long-lasting (approximately 30 min), reproducible electrochemical signals in the VB which were suppressed by alpha-MPT or FLA-63. These studies provide in vivo evidence which suggests that stressful somatosensory input to the VB initiates the release of NE.

Animals↗

PubMed1992

A microcomputer program for determining turnover rates during non-steady state conditions: application to monoamine turnover.

A program to calculate the turnover rate of monoaminergic neurotransmitters was written for use on microcomputers. The program is based on non-steady state models, i.e., measuring the rate of change of levels of neurotransmitters or their metabolites after pharmacological inhibition of synthetic or degradative enzymes. Methods have been developed to estimate monoamine turnover by measuring the rate of decrease of catecholamine levels after treatment with alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, or the increase in serotonin levels after pargyline, an inhibitor of monoamine oxidase. This program is suitable for examining either linear increases or exponential decreases in monoamine levels. The program has been tested in our laboratory for the determination of serotonin, dopamine or norepinephrine turnover after hormonal or pharmacological manipulations. The program is readily adaptable for calculation of the turnover rate of other biological molecules under non-steady state conditions.

Biogenic Monoamines↗