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C A Marsden

Publications and source records attributed to C A Marsden.

At least 127 records · Page 7Linked to original sources
PubMed1991

Neurotensin causes a greater increase in the metabolism of dopamine in the accumbens than in the striatum in vivo.

Differential pulse voltammetry with carbon fibre electrodes was used to study the effect of central administration of neurotensin on the extracellular level of 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum in anaesthetised rats. Intracerebroventricular injection of neurotensin (10 micrograms) increased the peak height for DOPAC 20 min after administration in the nucleus accumbens but only after 40 min in the striatum. The maximum increase was similar in both regions, with 30% and 27% above the pre-injection basal level, respectively. Neurotensin (1 micrograms) however increased the extracellular level of DOPAC in the nucleus accumbens alone. Neurotensin (0.1, 1.0 and 3.0 micrograms/0.5 microliter), injected into the ventral tegmental area, induced a potent and long-lasting elevation of the peak height for DOPAC in the nucleus accumbens, while the same doses in the substantia nigra produced effects on the metabolism of dopamine in the striatum of smaller amplitude and shorter duration. The maximum effect of each dose was about 2.5 times greater in the mesolimbic, compared to the nigrostriatal system. Amphetamine (2 mg/kg, s.c.) decreased the extracellular level of DOPAC with a similar magnitude, both in the nucleus accumbens (52%) and the striatum (47%). Intracerebroventricular administration of neurotensin (1 micrograms), 5 min after amphetamine, did not alter the effect of amphetamine on the extracellular level of DOPAC either in the nucleus accumbens or the striatum. However, neurotensin (10 micrograms) partially reversed the effect of amphetamine in the nucleus accumbens and had a similar but smaller and delayed effect in the striatum. The results from the present study, together with previous neurobehavioural studies, suggest that neurotensin has a relatively selective action on the mesolimbic dopaminergic system in the rat.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Posterior hypothalamic receptors involved in the cardiovascular changes elicited by electrical stimulation of the rostral ventrolateral medulla.

The posterior hypothalamic receptors involved in the cardiovascular responses to electrical stimulation of the rostral ventrolateral medulla were investigated in urethane-anaesthetized rats. Electrical stimulation of the rostral ventrolateral medulla produced a significant increase in systolic blood pressure. This response was significantly attenuated by the prior administration of d,l-propranolol (20 micrograms), clonidine (8 micrograms), atropine (8 micrograms) or methysergide (10 micrograms) into the posterior hypothalamus, but not by cimetidine (11 micrograms), chlorpheniramine (12 micrograms), naloxone (10 micrograms) or a vasopressin V1 antagonist (100 ng). The effect of clonidine (8 micrograms) on the pressor response to stimulation of the rostral ventrolateral medulla was antagonized by idazoxan (66 micrograms). These results confirm that the cardiovascular changes elicited by stimulation of the rostral ventrolateral medulla area are, in part, centrally modulated by alpha 2 and beta-adrenoceptors in the posterior hypothalamus which exert respectively, inhibitory and stimulatory effect. Furthermore the results indicate the involvement of posterior hypothalamic cholinergic and serotonergic receptors in the pressor response produced by stimulation of the rostral ventrolateral medulla.

Adrenergic alpha-Antagonists↗
PubMed1991

Resocialisation of isolation-reared rats does not alter their anxiogenic profile on the elevated X-maze model of anxiety.

Rats were reared from weaning either in isolation or in social groups for 30 days and their behaviour on the elevated X-maze was studied. Isolation-reared rats displayed an anxiogenic profile on the X-maze compared to socially reared controls. Resocialisation of isolation-reared rats for a further 30 days did not reverse this anxiogenic profile, and isolation of the socially reared rats for 30 days did not produce an anxiogenic behavioural profile, indicating that the differences observed may be a result of a permanent developmental change. The locomotor hyperactivity induced by isolation was specific to the rearing conditions. It remains to be determined what neurochemical events are involved in the sustained effects of rearing in isolation.

Aging↗
PubMed1991

Neuropeptides can interfere with the recording properties of voltammetric carbon fibre electrodes.

The effects of neuropeptides on the recording properties of carbon fibre micro-electrodes used with differential pulse voltammetry were examined both in vitro and in vivo. The in vitro voltammetric signal recorded in a solution containing 3,4-dihydroxyphenylacetic acid (10(-4) M) was attenuated after the addition of thyrotropin releasing hormone, neuromedin N and neurotensin (10(-5) M). The administration of neurotensin (1 or 3 micrograms/microliters) into the nucleus accumbens adjacent to the carbon fibre electrode produced a decrease in the extracellular 3,4-dihydroxyphenylacetic acid peak. However, evidence was obtained that peptides alter the recording properties of the microelectrodes when present at sufficient concentrations and such an effect may explain the result obtained in vivo. In contrast, neurotensin administered into the ventral tegmental area increased the 3,4-dihydroxyphenylacetic acid peak in the nucleus accumbens as previously reported. Thus, attenuation of the voltammetric signal was caused by an effect of the peptide on the recording properties of the electrode rather than real diminution of the free oxidisable amine around the electrode. Caution should be taken when investigating the effects of peptides on extracellular amines or their metabolites using in vivo voltammetry with carbon fibre electrodes if the peptides are administered in high concentrations close to the electrode.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Characterization of the 5-HT receptor subtypes involved in the motor behaviours produced by intrathecal administration of 5-HT agonists in rats.

1. The motor behavioural effects of intrathecal injections of 5-hydroxytryptamine (5-HT) and a variety of 5-HT receptor agonists were examined in adult Wistar rats to establish; (a) which 5-HT receptor subtype/s elicit each behaviour and (b) whether these receptors are located within the spinal cord. 2. Intrathecal injection of 5-methoxy-N,N'-dimethyltryptamine (5-MeODMT), (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) or 2,5-dimethoxy-alpha,4-dimethylbenzene ethamine hydrochloride (DOM) produced dose-related back muscle contractions (BMC) and wet dog shakes (WDS) which were both markedly attenuated by intraperitoneal pretreatment with either ritanserin (1 mg kg-1), ketanserin (0.16 mg kg-1) or mianserin (0.6 mg kg-1) indicating the involvement of 5-HT2 receptors in both these motor behaviours. Both fluoxetine (1-20 mg kg-1, i.p.) and high doses of 5-HT (50 micrograms) following fluoxetine (5 mg kg-1, i.p.) also elicited BMC, further confirming the involvement of 5-HT in this behaviour. 3. Intrathecal 5-carboxamidotryptamine (5-CT) evoked a marked wet-dog shake response without producing any BMC. Intrathecal pretreatment with 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) enhanced, while in contrast 2-methyl-5-HT pretreatment attenuated, 5-HT agonist-induced BMC without affecting WDS. These data suggest that the spinal 5-HT2 receptors mediating BMC are positively modulated by 5-HT1A but negatively influenced by 5-HT3 receptor activation and may be of a different subtype to the supra-spinal 5-HT2 receptors which elicit WDS. 4. A contrast, reciprocal forepaw treading, lateral head weaving, flat body posture and Straub-tail were evoked by 5-MeODMT, 8-OH-DPAT or 5-CT but not by DOI or DOM indicating that these behaviours were not produced by 5-HT2 receptor activation alone. Ritanserin (1 mg kg- 1, i.p.) or ketanserin (0.16mgkg-1, i.p.) pretreatment reduced the reciprocal forepaw treading induced by high intrathecal doses of either 5-MeODMT (25.pg) or 5-CT (50,ug) suggesting that this behaviour may be facilitated by 5-HT2 receptor activation. 5. Intrathecal injection of 5-HT (0.05-50pg, after systemic fluoxetine, 5mg kg 1, i.p.), or 1-(3-chlorophenyl) piperazine (mCPP) produced dose-related forepaw-licking and grooming, neither of which were attenuated by ketanserin (0.16 mgkg-1, i.p.) pretreatment suggesting these behaviours may be mediated by 5-HT1c receptors. In contrast, 2-methyl-5-HT (50 and 100pg) produced sideward tail-flicks, not evoked by any other 5-HT agonist and could therefore be mediated by spinal 5-HT3 receptor activation. 6. These data provide behavioural evidence for the existence of spinal 5-HT2 receptors which produce a novel motor behaviour, BMC. Ligand binding studies and dose-response studies with a range of selective 5-HT antagonists are required to establish whether BMC and WDS are mediated by different subtypes of 5-HT2 receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Muscarinic antagonists attenuate the increase in accumbens and striatum dopamine metabolism produced by clozapine but not by haloperidol.

1. The effect of the muscarinic antagonists, scopolamine and atropine, were examined on the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) in the nucleus accumbens and the striatum induced by haloperidol and clozapine by use of in vivo differential pulse voltammetry with carbon fibre electrodes in anaesthetized rats. 2. Animals received saline (1 ml kg-1, s.c.), scopolamine (1 mg kg-1, o.p.) or atropine (20 micrograms, i.c.v.) followed 15 min later by saline (10 microliters, i.c.v.), haloperidol (1 mg kg-1, s.c.) or clozapine (30 mg kg-1, i.p.) and extracellular DOPAC was simultaneously recorded in the nucleus accumbens and the striatum every 5 min for 60 min after drug administration. 3. Scopolamine or atropine alone had no effect on the DOPAC peak height but attenuated the increase in extracellular DOPAC induced by clozapine in both brain regions. Neither scopolamine nor atropine altered the haloperidol-induced increase in accumbens or striatal extracellular DOPAC. 4. The present results demonstrate that muscarinic antagonists attenuate the increase in accumbens and striatal dopamine metabolism in vivo produced by the atypical neuroleptic clozapine but not the haloperidol-induced increase in dopamine metabolism. The results indicate that central muscarinic receptors are involved in the actions on dopaminergic function of clozapine but not haloperidol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

In vivo neurochemical and behavioural effects of intracerebrally administered neurotensin and D-Trp11-neurotensin on mesolimbic and nigrostriatal dopaminergic function in the rat.

The effects of intracerebral application of neurotensin on the behavioural responses to peripheral dopamine agonist administration to rats, and on the levels of DOPAC voltammetrically determined in the striatum and nucleus accumbens of the anaesthetized rat have been examined. Bilateral application of neurotensin to the nucleus accumbens, like the neuroleptic haloperidol, inhibited the hyperactivity response to the dopamine agonist, n,N-propylnorapomorphine, but, unlike haloperidol, its bilateral intrastriatal application failed to reduce the degree of stereotyped behaviour induced by peripheral apomorphine injection. In the halothane-anaesthetized rat, neurotensin, when applied to the ventral tegmental area, stimulated DOPAC production in the ipsilateral nucleus accumbens, while its application to the substantia nigra did not affect striatal DOPAC levels significantly. Following its intracerebroventricular injection, however, DOPAC levels were considerably enhanced in both regions. The 11-D-tryptophan-substituted analogue of neurotensin potently mimicked the effects of the peptide itself in all studies. The findings of these investigations further confirm in vivo that the functional antagonism of dopamine by neurotensin is selective for the mesolimbic system, and that the effects of neurotensin can be correlated with reports on the regional distribution of its high-affinity binding sites in the rat brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Increased sensitivity to amphetamine and reward-related stimuli following social isolation in rats: possible disruption of dopamine-dependent mechanisms of the nucleus accumbens.

These experiments compared isolation-reared and socially-reared rats in two complementary paradigms for measuring responding to signals of reward, both undrugged and following either systemic or intraaccumbens d-amphetamine (AMPH). In experiment 1, locomotor activity conditioned to food presentation was measured in rats exposed to a restricted feeding schedule. The interaction between this conditioned activity, AMPH administration (0.5, 2.0, 3.5, 5.0 mg/kg IP) and motivational state was measured. In experiment 2, hungry rats were trained to associate a compound light/noise stimulus with sucrose reward and were then implanted with guide cannulae in the nucleus accumbens. In the test phase, responding on one of two novel levers produced the compound stimulus (conditioned reinforcer; CR). Responses on the other lever had no effect. Each rat received four counterbalanced intra-accumbens infusions of AMPH (0, 3, 10, 20 micrograms). In both experiments, isolated rats responded more with stimuli associated with reward and this differential rearing effect was further exaggerated by AMPH. The isolation-induced sensitivity to these stimuli and to AMPH was critically dependent on motivational variables. Thus, in experiment 1 there were no differences between the groups when sated or during extinction and in experiment 2 the increased responding was restricted to the lever providing CR. Measurements of the locomotor response to intra-accumbens AMPH (0, 3, 10 micrograms) also revealed that isolated rats were more sensitive to a low dose of the drug when tested food-deprived in a relatively novel environment. These results suggest that the experience of isolation-rearing interacts either directly or indirectly with dopamine-dependent mechanisms of the nucleus accumbens to enhance the effects of reward-related stimuli.

Animals↗
PubMed1990

Chronic 5-HT2 receptor antagonist treatment alters 5-HT1A autoregulatory control of 5-HT release in rat brain in vivo.

Rats treated chronically (14 days) with the 5-HT2 receptor antagonist ritanserin, show decreased 5-HT2 receptor numbers in the frontal cortex. The present experiments were designed to investigate the effects of acute and chronic ritanserin treatment on the autoregulatory control of the release of 5-HT and its metabolite 5-HIAA in vivo in rats using intracerebral dialysis. Neither acute nor chronic ritanserin treatment altered basal extracellular levels of 5-HT or 5-HIAA, suggesting that 5-HT2 receptors do not directly influence 5-HT release. In the control animals, systemic stimulation of somatodendritic 5-HT1A receptors with the 5-HT1A receptor agonist 8-OH-DPAT, inhibited the release of 5-HT presumably via inhibitory feedback autoregulation; an effect also seen in animals treated acutely with ritanserin. However, in the animals treated chronically with ritanserin, administration of 8-OH-DPAT produced an initial increase in extracellular 5-HT which declined gradually to the end of the experiment. These results suggest that chronic, but not acute, 5-HT2 receptor antagonist treatment attenuates the 5-HT1A receptor-mediated autoregulation of 5-HT release. The underlying mechanisms have yet to be ascertained.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

In vivo evidence that 5-hydroxytryptamine (5-HT) neuronal firing and release are not necessarily correlated with 5-HT metabolism.

The relationship between 5-hydroxytryptamine release, metabolism and unit activity has been investigated in the anaesthetized rat. 5-Hydroxytryptamine release and metabolism were monitored in vivo by the measurement of extracellular 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the frontal cortex using in vivo voltammetry combined with nafion-coated and uncoated electrically pretreated carbon fibre electrodes. The monoamine oxidase inhibitor pargyline (100 mg/kg) increased extracellular 5-hydroxytryptamine and decreased 5-hydroxyindoleacetic acid. The 5-hydroxytryptamine releaser fenfluramine (10 mg/kg i.p.) acutely increased extracellular 5-hydroxytryptamine while having no effect on 5-hydroxyindoleacetic acid and the effect on extracellular 5-hydroxytryptamine was markedly reduced in rats pretreated (four weeks) with 5,7-dihydroxytryptamine. 8-Hydroxy-2-(di-n-propyl-amino) tetralin (10 micrograms/kg i.v.), an agonist at the 5-hydroxytryptamine1A somatodendritic autoreceptor, inhibited 5-hydroxytryptamine neuronal firing in the dorsal raphe nucleus and decreased extracellular 5-hydroxytryptamine during the period when firing was inhibited but did not alter extracellular 5-hydroxyindoleacetic acid. In contrast 5-methoxy-3-(1,2,3,6-tetrahydro-4-pyridin-4-yl) (RU 24969), which is an agonist at the terminal autoreceptor in the rat, had no effect on 5-hydroxytryptamine neuronal firing but decreased 5-hydroxytryptamine and 5-hydroxyindoleacetic acid. The results support the view that extracellular 5-hydroxyindoleacetic acid is not a good index of 5-hydroxytryptamine release and that under specific circumstances 5-hydroxytryptamine neuronal firing, release and metabolism are independent of one another.

Action Potentials↗
PubMed1990

Biochemical and in vivo voltammetric evidence for differences in striatal dopamine levels in inbred strains of mice.

High performance liquid chromatography with electrochemical detection and differential pulse voltammetry were used to provide a direct measurement of tissue content of dopamine and its metabolites and extracellular dopamine levels, respectively, in the striata of BALB/c and CBA inbred strains of mice. We found that levels of striatal dopamine and its metabolite, dihydroxyphenylacetic acid, were significantly higher in the CBA strain than in the BALB/c strain, whereas levels of homovanillic acid were not significantly different between the strains. Levels of the dopamine metabolite 3-methoxytyramine, on the other hand, were higher in the BALB/c mice. Dopamine turnover rates were significantly higher in the CBA strain when the homovanillic acid/dopamine ratio was used as an index of dopamine activity. Voltammetric recording showed that the local infusion of K+ in pargyline-treated mice resulted in the immediate appearance of a peak at +85 mV, which has been shown to correspond to extracellular dopamine in the rat. The mean height of this peak detected in vivo following K+ stimulation corresponds to in vitro dopamine concentrations of 25 +/- 8 microM for BALB/c mice and 7 +/- 2 microM for CBA mice. K(+)-stimulated dopamine release in the BALB/c mice could be evoked every 10-15 min with similar magnitude. In contrast, very little dopamine release in CBA mice could be evoked after the first stimulation. Since striatal dopamine levels are higher in CBA mice, these data suggest that (a) BALB/c strain may have more dopamine in the readily releasable pool, whereas the CBA mice have a larger storage pool of dopamine, and/or (b) that dopamine uptake in the CBA mice is much more avid than in BALB/c.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effects of a selective 5-HT2 agonist, DOI, on 5-HT neuronal firing in the dorsal raphe nucleus and 5-HT release and metabolism in the frontal cortex.

Systemic administration of the 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (50 and 100 micrograms kg-1, i.v.) inhibited dorsal raphe neuronal firing. DOI (100 micrograms kg-1, i.v.) also produced a decrease in extracellular 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in the frontal cortex measured by microdialysis. However, local administration of DOI into the frontal cortex produced no change in extracellular 5-HT and 5-HIAA at any dose given (1, 10 and 100ng). The results demonstrate that DOI is a potent inhibitor of 5-HT neuronal firing and terminal release and that the effects on release are not mediated by an action within the terminal region. The site of action and the receptor involved in the inhibition remains to be determined.

Amphetamines↗
PubMed1990

The pharmacology of new anxiolytics acting on 5-HT neurones.

This paper discusses the alternative approaches available for the development of anxiolytics not acting on the benzodiazepine--GABA receptor complex. There are now several compounds that work by reducing 5-hydroxytryptamine function in the brain that have been shown to have anxiolytic properties in animals and in some cases man. Detailed long-term clinical trials are required to determine whether these new drugs are clinically useful and avoid the problems associated with benzodiazepines.

Animals↗
PubMed1989

Measurement of 3-methoxytyramine by in vivo voltammetry: evidence for differences in central dopamine function in BALB/c and CBA mice.

Differential pulse voltammetry (DPV) combined with carbon fibre electrodes allows selective detection of electroactive dopamine and serotonin metabolites in vivo. While usually employed in rats, we have now applied this in vivo technique in two inbred strains of mice: BALB/c and CBA. Three distinct oxidation peaks were recorded in vivo in the striatum of either BALB/c or CBA mice with a small shoulder occurring after the third peak at approximately +400 mV. Pargyline (150 mg/kg i.p.) potentiated this voltammetric shoulder into an easily measurable peak (Peak 4). In addition, Peak 4 was 2-3 times larger in BALB/c than in CBA mice. Homovanillic acid (HVA) and 3-methoxytyramine (3-MT), both catabolites of dopamine, oxidised at approximately +400 mV in vitro. Brain tissue levels of HVA and 3-MT, measured by high-performance liquid chromatography (HPLC) with electrochemical detection, demonstrated that pargyline treatment reduced striatal HVA, but increased 3-MT. These results support the view that Peak 4 recorded in the striatum of pargyline-treated mice in vivo is due to the oxidation of extracellular 3-MT. Thus, Peak 4 may be a useful index of dopamine release in situations where dopamine itself cannot be detected. Local infusion of KCl (2 microliters, 0.1 M) further increased the size of Peak 4 in the striatum of both BALB/c and CBA mice. However, the increase was approx. 3 times greater in BALB/c mice, supporting previous evidence of greater dopaminergic function of BALB/c compared with CBA mice. In addition these two inbred strains of mice provide model systems for investigating the comparative functional roles of nigrostriatal pathways.

Animals↗
PubMed1989

Effects of a sedative and of a non-sedative H1-antihistamine on the event-related potential (ERP) in normal volunteers.

Measurements of the amplitude and latency of the P3b component of the event-related potential (ERP), simple reaction time (SRT) and four psychomotor tests (VAS, DSST, DSp and CFF) were made on 12 male subjects (aged 19-24 years) 1.0-1.5 and 4.0-4.5 h after single oral doses of triprolidine (7.5 mg), terfenadine (60 mg) and placebo. Neither triprolidine nor terfenadine changed P3b amplitude or latency although VAS, CFF and DSST scores were significantly altered by triprolidine at 1.0-1.5 h after dosage. These results suggest that the P3b is too robust to reflect the mild sedative properties of an H1-receptor antihistamine, or that H1-receptors are not involved in P3b generation.

Adult↗
PubMed1989

The effects of chronic treatment with amitriptyline and MDL 72394 on the control of 5-HT release in vivo.

The purpose of the experiments reported were to determine whether chronic treatment with either a monoamine oxidase (MAO) inhibitor or an uptake inhibitor would increase extracellular levels of 5-HT in vivo and whether such treatment resulted in a down-regulation of the 5-HT1B-mediated decrease in extracellular levels of 5-HT. Rats were given either saline, (E)-beta-fluoromethyline-m-tyrosine (MDL 72394 0.25 mg/kg p.o.) or amitriptyline (10 mg/kg p.o.) once a day for 21 days. Twenty-four hr after the final injection, dialysis loops were implanted into the frontal cortices of these rats and basal extracellular levels of 5-HT were measured. The effect of the 5-HT1 receptor agonist 5-methoxy-3(1,2,3,6-tetrahydropyridin-4-yl)1H indole succinate (RU 24969 10 mg/kg i.p.) on the extracellular level of 5-HT was then studied. Basal levels of 5-HT in saline-treated rats was found to be 27.9 +/- 3.9 fmol/20 microliters perfusate. Chronic treatment with amitriptyline had no effect on extracellular levels of 5-HT but chronic treatment with MDL 72394 significantly increased extracellular levels of 5-HT. Chronic treatment with either MDL 72394 or amitriptyline had no significant effect on the ability of RU 24969 to reduce extracellular levels of 5-HT. These results suggest that 5-HT1B receptors are not down-regulated in response to chronically raised extracellular levels of 5-HT.

Amitriptyline↗
PubMed1989

Comparative behavioural and biochemical effects of repeated intrathecal administration of thyrotrophin-releasing hormone (TRH) or two analogues of TRH in adult rats.

The effect of repeated intrathecal injection of thyrotrophin-releasing hormone (TRH) and two analogues of TRH, C-terminally modified RX 77638 and N-terminally modified CG 3509, were examined on behavioural (wet-dog shakes and forepaw licking) and biochemical markers for spinal motoneurones, bulbospinal raphe nerve terminals and the pituitary-thyroid axis in rats. Saline (10 microliters washed in with 15 microliters), TRH (20 micrograms), RX 77368 (2 micrograms) or CG 3509 (2 micrograms) were administered intrathecally (twice daily for 3 or 5 days), after which levels of plasma-free thyroxine and thyroid-stimulating hormone (TSH) were measured and the dorsal and ventral portions of the thoracolumbar spinal cord, brainstem and hypothalamus were assayed for TRH- and calcitonin gene-related peptide (CGRP)-like immunoreactivity, levels of indoleamines and the activity of choline acetyltransferase (ChAT). Behavioural tolerance developed rapidly with consecutive injections of RX 77368, such that wet-dog shakes were significantly reduced and forepaw-licking tended to be decreased by the third intrathecal injection. Five, but not 3, days of administration of RX 77368 selectively elevated levels of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid in the ventral spinal cord, where these substances are principally located in bulbospinal raphe nerve terminals. The time course of the change in indoleamines suggests that administration of TRH peptides elevated the synthesis, rather than the release, of 5-HT from these nerve terminals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗