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M Y Ho

Publications and source records attributed to M Y Ho.

At least 37 records · Page 2Linked to original sources

5-hydroxytryptamine and impulse control: prospects for a behavioural analysis.

Impulsiveness is a significant clinical problem associated with a variety of psychiatric and neuropsychiatric disorders. Clinical and experimental studies have provided evidence that individuals displaying impulsive behaviour tend to show signs of deficient functioning of the ascending 5-hydroxytryptaminergic (5-HTergic) pathways of the brain. A persistent problem in investigations of the biological basis of impulsive behaviour has been the lack of a satisfactory definition of 'impulsiveness', as distinct from other behavioural features, such as aggression, which are often apparent in 'impulsive' individuals. Research in the experimental analysis of behaviour suggests that two important characteristics of 'impulsiveness' are (i) deficient tolerance of delay of gratification and (ii) inability to inhibit or delay voluntary behaviour; both of these characteristics are amenable to study in laboratory animals. We describe some delayed reinforcement and delayed response paradigms which purport to capture these behavioural characteristics, and review recent evidence that manipulation of 5-HTergic function alters behaviour in these paradigms. It is argued that the two characteristics of 'impulsiveness' are themselves the product of disturbance of more fundamental behavioural processes; the nature of these processes is considered.

Animals↗

A bovine oxytocin transgene in mice: expression in the female reproductive organs and regulation during pregnancy, parturition and lactation.

Transgene bovine oxytocin 3.5 (bOT3.5) consists of the bovine oxytocin structural gene flanked by 0.6 kbp of upstream and 1.9 kbp of downstream sequences. We have examined the expression of bOT3.5 in the female reproductive organs, and we show tissue-specific and physiological regulation dependent on the stage of pregnancy and lactation. In the ovary, no transgene expression could be detected during the estrus cycle, or during pregnancy. However, high levels of transgene RNA were found at day 1 of lactation. Expression dropped 10-fold by day 2 of lactation, and was undetectable thereafter. Interestingly, the expression of bOT3.5 in the mouse ovary at the beginning of lactation mimics that of the endogenous OT gene in the bovine ovary. Expression of the bOT3.5 transgene correlates with a parturition defect that results in considerable maternal mortality.

Animals↗

Effect of destruction of the 5-hydroxytryptaminergic pathways on temporal memory: quantitative analysis with a delayed interval bisection task.

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on memory for duration, using a delayed interval bisection task. Rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats, were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus, and lever B following an 8-s presentation of the same stimulus. Following stimulus offset a response on a panel placed midway between the two levers was required in order to initiate lever presentation; a single response on either lever resulted in withdrawal of both levers and, in the case of a "correct' response, reinforcer delivery. When > 90% correct choices had been attained, an 8-s (phase I) or a 12-s (phase II) delay was interposed between stimulus offset and lever presentation in 50% of the trials, and probe trials (10% of both non-delay and delay trials) were introduced in which the light was presented for intermediate durations. Logistic functions were derived relating percent choice of lever B to stimulus duration. In both groups, the imposition of post-stimulus delays displaced the bisection point (duration yielding 50% choice of lever B) towards longer durations; this effect was significantly greater in the lesioned group than in the control group. Imposition of post-stimulus delays resulted in increases in the Weber fraction, which did not differ significantly between the two groups. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered.

5,7-Dihydroxytryptamine↗

Destruction of central noradrenergic neurones with DSP4 impairs the acquisition of temporal discrimination but does not affect memory for duration in a delayed conditional discrimination task.

This experiment examined the effect of destroying central noradrenergic neurones using the selective neurotoxin N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine (DSP4) on the acquisition of a temporal discrimination and on memory for duration, using a delayed conditional discrimination task. In phase I, rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus, and lever B following an 8-s presentation of the same stimulus. Following stimulus offset, a response on a panel placed midway between the two levers was required to initiate lever presentation; a single response on either lever resulted in withdrawal of both levers and, in the case of a "correct" response, reinforcer delivery. Both groups acquired accurate discrimination, achieving 90% correct choices within 50 sessions; the DSP4-treated group acquired accurate performance more slowly than the control group. In phase II, delays were interposed between stimulus offset and lever presentation in 50% of the trials. In the absence of a delay, discriminative accuracy was lower in the DSP4-treated group than in the control group. Accuracy declined as a function of post-stimulus delay in both groups; both groups showed a delay-dependent bias towards responding on lever A ("choose-short" bias). Neither of these effects differed significantly between the two groups. The concentrations of noradrenaline in the parietal cortex and hippocampus were reduced by 90% and 89% in the DSP4-treated group, compared to the levels in the control group, but the levels of dopamine, 5-hydroxytryptamine and 5-hydroxyindoleacetic acid did not differ significantly between the groups. The results confirm the deleterious effect of DSP4 on the acquisition of temporal discrimination, but do not provide evidence for a role of the noradrenergic innervation of the hippocampus and neocortex in temporal working memory.

5,7-Dihydroxytryptamine↗

Effect of central 5-hydroxytryptamine depletion on performance in the "time-left" procedure: further evidence for a role of the 5-hydroxytryptaminergic pathways in behavioural "switching".

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule: the "time-left" procedure. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained in a discrete trials schedule in which reinforcers were provided for responding on either of two levers, A and B. At a random time point, t s after the start of each trial, a response on A resulted in the delivery of one food pellet after dA s, whereas a response on B resulted in the delivery of two pellets after 60-t s. The value of dA was varied between 1 and 8 s in different phases of the experiment. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time within the trial. An index of timing (T75: the time within the trial at which relative response rate on B attained a value of 75%) was systematically related to the value of dA, but did not differ significantly between lesioned and control rats. However, the lesioned group showed significantly higher rates of switching between response alternatives than the sham-lesioned group at all values of dA. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results provide further evidence that the ascending 5HTergic pathways may contribute to the inhibitory regulation of switching between behavioural states.

5,7-Dihydroxytryptamine↗

Repression of vasopressin gene expression by glucocorticoids in transgenic mice: evidence of a direct mechanism mediated by proximal 5' flanking sequence.

Glucocorticoids are known to exert multiple effects upon neuronal systems and neuronal gene expression but the molecular mechanisms through which these effects are mediated are largely undefined. In this study, a transgenic mouse model that expresses a bovine vasopressin transgene was used to investigate the mechanisms by which this neuropeptide gene is repressed by glucocorticoids. Using both northern analysis and a reverse transcriptase polymerase chain reaction assay, depletion of glucocorticoids with the 11,beta-hydroxylase inhibitor metyrapone was shown to result in a dexamethasone-reversed increase in ectopic adrenal transgene messenger RNA levels. This result shows that sequences within the confines of the 3.5 kb transgene are sufficient to mediate repression by glucocorticoids, and indicates the involvement of a type II glucocorticoid receptor mechanism which is independent of cellular context. Evidence for the involvement of cis-acting repressive elements in the proximal 5' flanking sequence was obtained in further studies in which bovine transgene constructs were shown to be negatively regulated by dexamethasone in 293 cells. The further demonstration that recombinant glucocorticoid receptor binds to a vasopressin promoter fragment in an in vitro electrophoretic mobility shift assay provided additional evidence of a direct mechanism of repression. Both in vitro studies were consistent with the presence of a glucocorticoid regulatory element within the region -300 to 155 of the transcription start site. The use of an in vivo transgenic system combined with in vitro analyses of gene promoter fragments enabled the characterization of the molecular mechanisms which effect physiological changes in vasopressin gene expression, and provided evidence of a direct mechanism of repression mediated by sequences within the vasopressin gene promoter.

Animals↗

Inhibition of bradykinin-induced calcium increase by phosphatase inhibitors in neuroblastoma x glioma hybrid NG108-15 cells.

Prior treatment of NG108-15 cells with phosphatase inhibitors including okadaic acid and calyculin A inhibited the elevation of cytosolic Ca2+ concentration ([Ca2+]i) induced by bradykinin by approximately 63%. This inhibition was dependent on the concentration of okadaic acid with an IC50 of 0.15 nM. Okadaic acid treatment only lowered the maximal response of [Ca2+]i increase and had no effect on the EC50 value for bradykinin regardless of the presence of extracellular Ca2+. Neither the capacity of 45Ca2+ accumulation within intracellular nonmitochondrial Ca2+ stores nor the magnitude of [Ca2+]i increase induced by thapsigargin was reduced by the treatment of okadaic acid. In contrast, the same phosphatase inhibitor treatment inhibited the bradykinin-evoked inositol 1,4,5-trisphosphate (IP3) generation, the Mn2+ influx, and the capacity of mitochondrial Ca2+ accumulation. Furthermore, the sensitivity of IP3 in the Ca2+ release was suppressed by okadaic acid pretreatment. Our results suggest that the reduction of bradykinin-induced [Ca2+]i rise by the promotion of protein phosphorylation was attributed to the reduced activity of phospholipase C, the decreased sensitivity to IP3, and the slowed rate of Ca2+ influx. Thus, phosphorylation plays a role in bradykinin-sensitive Ca2+ signaling cascade in NG108-15 cells.

Animals↗

Neurogenic diabetes insipidus in children with hypoxic encephalopathy: six new cases and a review of the literature.

UNLABELLED: Hypoxic encephalopathy is rarely mentioned as a cause of neurogenic diabetes insipidus (DI) in children. We here report six cases of DI which occurred after severe hypoxic/ischaemic brain damage and include a review of the literature on 28 paediatric cases of neurogenic DI due solely to severe hypoxia/ischaemia. Airway obstruction, haemorrhagic shock and sudden infant death syndrome are the three major causes of hypoxia/ischaemia. The ages (25/28) ranged from 0.03 to 18 years (mean 7.27 years, median 5 years). The intervals between the hypoxic insult and the onset of DI (23/28) ranged from 0.08 days (2 h) to 13 days (mean 4.07 days, median 3.5 days). Linear regression analysis revealed no significant correlation between the age and the interval. Nineteen cases (82.6%) developed DI within 6 days after the hypoxic/ischaemic insult. Only two neonates survived with developmental delay. The remaining 26 cases died. CONCLUSION: Neurogenic DI can be caused by hypoxia/ischaemia and is an ominous sign of severe brain damage in children with hypoxic encephalopathy. It is important to recognize this potential sequel by regularly monitoring intake and output, plasma sodium level, and urine specific gravity.

Adolescent↗

Pancreatitis in children--experience with 43 cases.

UNLABELLED: Pancreatitis in children is not common and can be associated with severe morbidity and mortality. We encountered 43 children, ranging in age from 2 to 18 years, with pancreatitis over the past 10 years. The diagnosis of pancreatitis was made in those patients who showed: (1) significant intra-operative pathology or; (2) clinical findings of pancreatic inflammation and laboratory confirmation. More than one third (16 cases) of the cases were due to trauma, other causes included systemic disease (10), structural disease (8), and toxins or drugs (4). Five cases were classified as idiopathic. Most of the patients presented with abdominal pain (95%) and vomiting (56%). Jaundice was found in 7 patients and an abdominal mass in 2. Morbidity included pseudocyst (10), relapse (4), hyperglycaemia (4) and miscellaneous problems. Eight (50%) of the patients with trauma and 6 (86%) of the patients with structural diseases required surgery. Other patients were managed conservatively with bowel rest, gastric decompression, intravenous fluid and total parenteral nutrition. One case had a fatal outcome. All the survivors did well in long term follow up. Relevant literature has been reviewed and the sensitivity of various diagnostic modalities compared and discussed. A lesser known association between pancreatitis and structural anomalies such as choledochal cyst is discussed. To our knowledge, the present review is the first on pancreatitis in Chinese children. CONCLUSION: Pancreatitis can occur from a wide variety of causes and may result in severe complications. Early diagnosis, close monitoring and aggressive intervention are mandatory to reduce morbidity and mortality.

Abdomen, Acute↗

Effect of destruction of the 5-hydroxytryptaminergic pathways on the acquisition of temporal discrimination and memory for duration in a delayed conditional discrimination task.

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on the acquisition of a temporal discrimination and on memory for duration, using a delayed conditional discrimination task. In phase I, rats that had received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei, and sham-lesioned control rats, were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus, and lever B following an 8-s presentation of the same stimulus. Following stimulus offset, a response on a panel placed midway between the two levers was required in order to initiate lever presentation; a single response on either lever resulted in withdrawal of both levers and, in the case of a "correct" response, reinforcer delivery. Both groups gradually acquired accurate discrimination, achieving > 90% correct choices within 20-30 sessions; the lesioned group acquired accurate performance significantly faster than the control group. In phase II, delays were interposed between stimulus offset and lever presentation in 50% of the trials (2, 4, 8, 16 and 32 s; 10% of trials in each case). Accuracy declined as a function of post-stimulus delay in both groups, and there was no significant difference between the performances of the two groups. Both groups showed an increasing tendency to respond on lever A following longer post-stimulus delays ("choose-short" effect); this effect was somewhat enhanced in the lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered.

Animals↗

Effects of desipramine and fluvoxamine on timing behavior investigated with the fixed-interval peak procedure and the interval bisection task.

Acute treatment with antidepressant drugs is known to increase the mean interresponse time (IRT) in the IRT > 72-s schedule of reinforcement. In order to examine the possibility that this effect may reflect an action of the antidepressants on timing processes, we tested the effects of two antidepressants, desipramine and fluvoxamine, on behaviour maintained under two other timing schedules in rats. In the fixed-interval peak procedure (fixed-interval 30-s), acute treatment with desipramine (8 mg kg-1) reduced response rate, whereas acute treatment with fluvoxamine (8 mg kg-1) increased it. Neither drug significantly altered the time to attainment of peak response rate or the Weber fraction. In the interval bisection task (standard durations 2 s and 8 s), the bisection point was not significantly altered by acute treatment with either drug. Chronic treatment with desipramine (8 mg kg-1 b.d.) had no effect on any of the indices of timing under either schedule. Chronic treatment with fluvoxamine (8 mg kg-1 b.d.) reduced the time to attainment of peak response rate but had no effect on the Weber fraction under the fixed-interval peak procedure, and did not alter the bisection point or Weber fraction under the interval bisection procedure. The failure of desipramine and fluvoxamine to increase the time to peak response rate or the bisection point at doses that significantly altered operant response rate suggests that the effect of these drugs on IRT schedule performance is unlikely to reflect an interaction with timing processes.

Adrenergic Uptake Inhibitors↗

Effect of destruction of the 5-hydroxytryptaminergic pathways on behavioural timing and "switching" in a free-operant psychophysical procedure.

This experiment examined the effect of destruction of the ascending 5-hydroxytryptaminergic (5HTergic) pathways on performance in a free-operant timing schedule. Rats received either injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for a sucrose reinforcer. Training sessions consisted of 40, 50-s trials in which reinforcers were available on a variable-interval 25-s schedule; in the first 25 s of each trial, reinforcers were only available for responses on lever A, whereas in the last 25 s reinforcers were available only for responses on lever B. Data were collected from probe trials (four per session) in which no reinforcers were delivered, during the last ten of 50 training sessions. Both groups showed decreasing response rates on lever A and increasing response rates on lever B as a function of time from the onset of the trial. Response rate on lever B, expressed as a percentage of overall response rate, could be described by a two-parameter logistic function; neither the indifference point (i.e. the time corresponding to 50% responding on lever B) nor the slope of the function different between the two groups. However, the lesioned group showed a higher rate of switching between response alternatives than the sham-lesioned group. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not significantly altered. The results confirm previous findings that behaviour in timing schedules is sensitive to destruction of the central 5HTergic pathways, and suggest that these pathways may contribute to the inhibitory regulation of switching between behavioural states.

5,7-Dihydroxytryptamine↗

Dopamine withdrawal elicits prolonged calcium rise to support prolactin rebound release.

Dopamine (DA) acts directly on pituitary lactotropes to inhibit the release of PRL. Removal of DA elicits a pronounced transient rise in PRL release to values exceeding pre-DA rates (PRL rebound). Electrophysiological studies have shown that lactotropes exhibit a period of increased Ca2+ action potential activity after DA withdrawal, leading to the proposal that enhanced Ca2+ influx during this period may support the rebound secretion of PRL. In the present studies, we investigated the effect of DA application and removal on the cytosolic free calcium concentration ([Ca2+]i) monitored by fura-2 in single rat lactotropes. Unchallenged lactotropes fell into two functionally distinct groups: those with stable [Ca2+]i that was not acutely sensitive to extracellular Ca2+, and those with spontaneous fluctuations in [Ca2+]i that were dependent upon influx of external Ca2+. There was striking variability in the [Ca2+]i patterns of the latter group, ranging from irregular, low amplitude fluctuations to rhythmic, repetitive oscillations with definable rise and decay kinetics. Application of DA resulted in a rapid decrease in [Ca2+]i concomitant with the cessation of these spontaneous [Ca2+]i fluctuations. After DA removal, these cells resumed oscillatory [Ca2+]i activities similar to those observed before DA application. In quiescent lactotropes, acute application of DA exerted no effect on resting [Ca2+]i, but quiescent cells could be activated to produce [Ca2+]i fluctuations by the application and withdrawal of DA. Again, the character of the induced [Ca2+] activity showed significant cell to cell variation. In contrast, the pattern of [Ca2+]i fluctuations was remarkably characteristic in a given cell in response to repeated challenges. A composite [Ca2+]i profile of 13 cells paralleled the PRL secretory rebound after application and removal of DA. The oscillatory rise in [Ca2+]i is functionally linked to the rebound release of PRL after DA removal, as both were immediately abolished by blockade of Ca2+ influx. These data demonstrate that the rebound secretion of PRL is dependent upon enhanced influx of extracellular Ca2+ after cells recover from DA-induced hyperpolarization and support the hypothesis that a population of inactivated Ca2+ channels has been recruited in response to application and withdrawal of DA.

Animals↗

Nitrite, N-nitroso compounds, and other analytes in physiological fluids in relation to precancerous gastric lesions.

Levels of gastric juice nitrite, several urinary N-nitroso compounds, and other analytes were examined among nearly 600 residents in an area of Shandong, China, where precancerous gastric lesions are common and rates of stomach cancer are among the world's highest. Gastric juice nitrite levels were considerably higher among those with gastric juice pH values above 2.4 versus below 2.4. Nitrite was detected more often and at higher levels among persons with later stage gastric lesions, especially when gastric pH was high. Of those with intestinal metaplasia, 17.5% had detectable levels of gastric nitrite, while this analyte was detected in only 7.2% of those with less advanced lesions. Relative to those with undetectable nitrite, the odds of intestinal metaplasia increased from 1.5 (95% confidence interval = 0.6-4.1) to 4.1 (95% confidence interval = 1.8-9.3) among those with low and high nitrite concentrations, respectively. Urinary acetaldehyde and formaldehyde levels also tended to be higher among those with more advanced pathology, particularly dysplasia. However, urinary excretion levels of total N-nitroso compounds and several nitrosamino acids differed little among those with chronic atrophic gastritis and intestinal metaplasia and dysplasia, consistent with findings from recent studies in the United Kingdom, France, and Colombia. The data from this high-risk population suggest that elevated levels of gastric nitrite, especially in a high pH environment, are associated with advanced precancerous gastric lesions, although specific N-nitroso compounds were not implicated.

Adult↗

Effects of extracellular ATP on Ca2+ mobilization in Madin Darby canine kidney (MDCK) cells.

Previous studies have demonstrated that ATP activates calcium-dependent K+ channels thereby leading to plasma membrane hyperpolarization and chloride secretion in MDCK cells. However, the signaling pathway involved in regulating ATP-evoked Ca2+ mobilization in MDCK cells remains unclarified. The present study was performed to elucidate the mechanisms underlying ATP-evoked calcium mobilization and inositol phospholipid turnover in MDCK cells. Our results indicate that ATP exerted its effects by activating the P2u subtype purinoceptor because both ATP and UTP but not adenosine caused Ca2+ mobilization. ATP induced [Ca2+]i increase in a dose-dependent manner with a maximal and half-maximal effect at 100 microM and 5 microM, respectively. In the absence of external Ca2+, both UTP and ATP were capable of mobilizing Ca2+ from internal stores through an IP3-sensitive pathway and the response for the former was larger than the latter. While in the presence of external Ca2+, the magnitude of UTP-induced [Ca2+]i increase was similar to that of ATP. These observations suggest that other mechanisms involved in addition to P2u subtype receptors in regulating ATP-induced Ca2+ response. The Ca2+ transients observed in Ma(2+)-depleted media were greater than those seen in Mg(2+)-contained media. ATP-induced Na+ influx were evidenced by SBFI loaded MDCK cells in Mg(2+)-depleted media. These data support that non-selective ATP4-membrane pores were formed under the application of ATP. The ATP-induced Ca2+ rise was suppressed by either omega-conotoxin or La3+ but was unaffected by the L-type Ca2+ channel blockers, verapamil and nifedipine. The deprivation of external Na+ also enhanced the ATP-induced Ca2+ rise. These data indicate that a P2 receptor-mediated cation channel was also involved under the stimulation of ATP.

Adenosine Triphosphate↗

Bovine oxytocin transgenes in mice. Hypothalamic expression, physiological regulation, and interactions with the vasopressin gene.

To gain insights into the molecular mechanisms that restrict the expression of the oxytocin gene to anatomically defined groups of neurons in the hypothalamus, we generated transgenic mice bearing bovine oxytocin genomic fragments. Appropriate neuron-specific and physiological regulation was observed in mice bearing transgene bOT3.5, which consists of the oxytocin structural gene flanked by 0.6 kilobase pair (kbp) of upstream and 1.9 kbp of downstream sequences. bOT3.5 is expressed in oxytocin magnocellular neurons in the mouse supraoptic nucleus and paraventricular nucleus, but transgene RNAs are excluded from vasopressin neurons. Replacement of the drinking diet of the transgenic mice with 2% (w/v) NaCl for 7 days significantly increased the abundance of bovine oxytocin transcripts in the supraoptic nucleus, but not in the paraventricular nucleus, in parallel with the endogenous mouse oxytocin RNA. Surprisingly, mimicry of the endogenous oxytocin gene expression pattern was lost with larger transgenes. Addition of 0.7 kbp of contiguous downstream sequences (transgene bOT) or linkage to the bovine vasopressin gene (transgene VP-B/bOT3.5) repressed hypothalamic expression. No mice were derived bearing transgene bOT6.4, which consists of the oxytocin structural gene flanked by 3 kbp of upstream and 2.6 kbp of downstream sequences, suggesting that the presence of this DNA is detrimental to normal embryonic development. These data suggest that while bOT3.5 contains sufficient cis-acting sequences to mediate expression to particular subsets of hypothalamic neurons, the overall regulation of the oxytocin gene is governed by multiple interacting enhancers and repressors.

Animals↗

Retarded acquisition of a temporal discrimination following destruction of noradrenergic neurones by systemic treatment with DSP4.

This experiment examined the effect of destroying central noradrenergic neurones, using the selective neurotoxin DSP4 (N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine) on the acquisition and performance of discrimination between two time intervals. Rats that had received systemic treatment with DSP4 and vehicle-treated control rats were trained in a series of discrete trials to press lever A following a 2-s presentation of a light stimulus and lever B following an 8-s presentation of the same stimulus. Both groups acquired the discrimination (> 90% correct choices) within 15 sessions; however, the DSP4-treated group showed significantly slower acquisition than the control group. When stable performance had been attained, 'probe' trials were introduced in which the light was presented for intermediate durations. Both groups showed sigmoid functions relating percent choice of lever B to log stimulus duration. Neither the bisection point (duration corresponding to 50% choice of lever B) nor the Weber fraction differed significantly between the DSP4-treated and control groups. The levels of noradrenaline were markedly reduced in the neocortex and hippocampus of the DSP4-treated group, but the levels of dopamine and 5-hydroxytryptamine were not altered. The results indicate that noradrenaline depletion induced by DSP4 retarded the acquisition of temporal discrimination, but did not impair steady-state discriminative precision.

Adrenergic Agents↗

The role of the ascending 5-hydroxytryptaminergic pathways in timing behaviour: further observations with the interval bisection task.

This experiment examined the effect of destroying the 5-hydroxytryptaminergic (5HTergic) pathways on rats' ability to discriminate between two durations. Rats received injections of 5,7-dihydroxytryptamine into the median and dorsal raphe nuclei or sham lesions. They were trained to press lever A following a 2-s presentation of a light and lever B following an 8-s presentation of the light. For some rats, the levers were inserted into the chamber immediately after stimulus presentation ("no-poke-requirement"); for others, the levers were not inserted until a flap covering the food tray positioned midway between the levers had been depressed ("poke-requirement"). When stable performance was attained, "probe" trials were introduced in which the light was presented for intermediate durations. Logistic functions were derived relating percent choice of lever B to log stimulus duration. Under the "no-poke-requirement" condition, the bisection point (duration yielding 50% choice of lever B) was shorter in the lesioned rats than in the control rats. Under the "poke-requirement" condition, this effect of the lesion was attenuated. There was no effect of the lesion on the Weber fraction under either condition. The levels of 5HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. It is proposed that rats may attain accurate timing under the interval bisection task by moving from one lever to the other during stimulus presentation; this movement may be facilitated by destruction of the 5HTergic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗