Biomedical subjects

C A Marsden

Publications and source records attributed to C A Marsden.

At least 109 records · Page 6Linked to original sources

PubMed1994

[The participation of the glutaminergic input of the nucleus accumbens in regulating the synaptic release of dopamine during associative learning].

The effect of MK-801 on basal and conditioned dopamine release in the rat n. accumbens, was studied. Exposure of the rats to the box where they had been given electrical shock, caused an immediate long lasting increase in the dopamine release. Administration of the MK-801 into the n. accumbens abolished the delayed increase in the dopamine release while exerting no effect on the immediate increase.

Animals↗

PubMed1993

Effect of diazepam on cortical 5-HT release and behaviour in the guinea-pig on exposure to the elevated plus maze.

Previous studies have used the elevated plus maze to test for "anxiolytic" drugs in rats. The present study demonstrates that guinea-pigs handled daily from birth exhibit similar behaviour to rats on the plus maze. Pretreatment with diazepam (1.0 mg/kg) significantly increased the time the animals spent in the open arms and amount of entries into the open arms. Using intra-cortical microdialysis on exposure of the guinea-pig to the elevated plus maze resulted in increased extracellular 5-HT in the frontal cortex. Diazepam reduced, but not significantly, the increase in extracellular 5-HT and produced an "anxiolytic" profile of behaviour. Pretreatment with the benzodiazepine antagonist flumazenil (10.0 mg/kg) fully antagonised the behavioural effects of diazepam. Flumazenil also reduced the effect of diazepam on the increase in extracellular 5-HT observed on exposure of the guinea-pig to the elevated plus maze. Flumazenil alone decreased basal extracellular cortical 5-HT but had no effect on behaviour in the elevated plus maze. The results show that an increase in extracellular 5-HT occurs in the guinea-pig exposed to aversive conditions. While it remains to be determined whether the "anxiolytic" effects of diazepam in the guinea-pig are causally associated with decreased extracellular 5-HT, it is of interest that the selective benzodiazepine antagonist also prevented the increase in basal extracellular 5-HT produced by the exposure to the elevated plus maze but had no effect on behaviour. Results indicate that there is no simple relationship between inhibition of 5-HT release and the "anxiolytic" action of benzodiazepines.

Animals↗

PubMed1993

Age-related behavioural, neurochemical and radioligand binding changes in the central 5-HT system of Sprague-Dawley rats.

Mature (3-4 months) and aged (18-19 months) Sprague-Dawley (SD) rats were treated with 5-HT receptor agonists and drug-induced behaviours monitored. The 5-HT2/1C agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), induced wet dog shakes and back muscle contractions which were significantly increased in aged, compared to mature, rats, suggesting an age-related enhancement of 5-HT2 receptor function. In contrast, the selective 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) induced forepaw treading, flat body posture, hypothermia and hyperactivity which were not significantly different in aged compared to mature rats. Levels of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus and frontal cortex were measured using high performance liquid chromatography with electrochemical detection. There were no age-related changes in hippocampal 5-HT or 5-HIAA. However both 5-HT and 5-HIAA were increased in the frontal cortex of aged SD rats. 8-OH-DPAT reduced 5-HIAA in both regions examined in mature rats, an effect which was attenuated in the aged rats, suggesting an age-related reduction in presynaptic 5-HT1A receptor function. DOI did not induce any changes in 5-HT or 5-HIAA in either of the regions examined. Radioligand binding studies with [3H] ketanserin showed there to be no significant age-related changes in cortical 5-HT2 receptor density or affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1993

Evidence that chronic administration of paroxetine or fluoxetine enhances 5-HT2 receptor function in the brain of the guinea pig.

The effects of chronic treatment with antidepressants on 5-HT-stimulated hydrolysis of phosphoinositide (PI) in the cerebral cortex of the guinea pig were examined. The pharmacological profile of the response was consistent with it being mediated by a 5-HT2 receptor. Chronic (but not acute) treatment with the selective 5-HT uptake inhibitors, paroxetine and fluoxetine (10 mg/kg, p.o., for 21 days), resulted in a significant increase in the maximum response to 5-HT without altering the EC50. There were no significant alterations in the density or affinity of 5-HT2 receptors, labelled with [3H]ketanserin. In contrast, treatment with the tricyclic antidepressant, amitriptyline (10 mg/kg, p.o., for 21 days), did not produce a significant change in 5-HT-stimulated hydrolysis of PI or in the number and affinity of 5-HT2 receptors. The findings are discussed in relation to the possible neurochemical targets for antidepressant drugs and species differences in the responses to these agents.

Amitriptyline↗

PubMed1993

Cocaine-induced behaviour: dopamine D1 receptor antagonism by SCH 23390 prevents expression of conditioned sensitisation following repeated administration of cocaine.

Repeated administration of cocaine (15 mg/kg) (once a week for 4 weeks, day 1, 7, 14 and 21) in a conditioned environment produced significant hyperactivity and head bobbing effects which showed sensitisation. Pretreatment with the D1 antagonist SCH 23390 (0.05 mg/kg), a dose that blocked d-amphetamine (2.5 mg/kg)-induced hyperactivity, antagonised the locomotor effects of cocaine after the second (day 7), third (day 14) and fourth (day 21) administration of cocaine but not the first day (day 1). Antagonism of head bobbing occurred on all 4 (1, 7, 14 and 21) days of treatment. In contrast, haloperidol (0.1 mg/kg) significantly reduced amphetamine-induced hyperactivity but potentiated the locomotor and stereotypic effects of cocaine, after administration of cocaine on days 1 and 7 and had no effect on cocaine-induced behaviour on days 14 and 21. The results suggest that the locomotor effects and head bobbing produced by cocaine, together with the expression of sensitisation to these effects in the conditioned environment, involve activation of post-synaptic D1 receptors. The potentiation of the effects of cocaine by a small dose of haloperidol may indicate increased release of dopamine due to blockade of pre-synaptic D2 autoreceptors.

Amphetamine↗

PubMed1992

Differential effects of amfonelic acid on the haloperidol- and clozapine-induced increase in extracellular DOPAC in the nucleus accumbens and the striatum.

This study compares the effects of the nonamphetamine stimulant amfonelic acid on the increase in extracellular 3,4-dihydroxyphenylacetic acid (DOPAC) induced by haloperidol and clozapine in the nucleus accumbens and the striatum of anaesthetized rats. DOPAC was simultaneously recorded in both regions using differential pulse voltammetry with electrically pretreated carbon fibre electrodes. Amfonelic acid (2.5 mg/kg s.c.) did not alter basal striatal DOPAC but produced a significant reduction in extracellular DOPAC in the nucleus accumbens. Haloperidol (1 mg/kg s.c.) increased extracellular DOPAC in both regions. When amfonelic acid was injected 5 min before haloperidol, the increase in DOPAC was potentiated in both the nucleus accumbens and the striatum but with a greater effect in the striatum. Clozapine (30 mg/kg i.p.) increased extracellular DOPAC in both regions, an effect partially attenuated by amfonelic acid in both regions but to a greater extent in the striatum. When ritanserin (5 mg/kg i.p.), a serotonergic antagonist (5-HT-2), was co-administered with haloperidol, the potentiation by amfonelic acid of the increase in extracellular DOPAC induced by haloperidol was attenuated in both the nucleus accumbens and the striatum. The present results confirm that amfonelic acid can be used to discriminate neurochemically between haloperidol and clozapine in vivo. The effects of amfonelic acid on the neuroleptic-induced changes in extracellular DOPAC were greater in the striatum than the nucleus accumbens. These results further demonstrate that both neuroleptics increase dopamine metabolism in the two brain regions but by different mechanisms, supporting the view that the regulation of dopamine metabolism differs in the two regions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Comparison of acute and chronic treatment of various serotonergic agents with those of diazepam and idazoxan in the rat elevated X-maze.

The aim of this study was to use the elevated X-maze to compare acute and chronic treatments of a 5-HT1A partial agonist, ipsapirone, a 5-HT2 antagonist, ritanserin, and a 5-HT3 antagonist, ondansetron, with those of established anxiolytic (diazepam) and anxiogenic (idazoxan) compounds. Acute diazepam (5 mg/kg IP) produced a significant increase in the percentage open:total entries and time and time spent in the end of the open arms (anxiolytic profile) on the elevated X-maze. Chronic treatment with diazepam (5 mg/kg IP twice daily for 14 days) still produced an anxiolytic profile which was not apparent 24 h after cessation of chronic treatment (withdrawal). In contrast, idazoxan given both acutely (0.25 mg/kg IP) and chronically (0.8 mg/kg/h at a flow rate of 5.5 microliters/h for 14 days, via osmotic minipumps) resulted in a significant decrease in the percentage open:total entries and time and time spent in the end of the open arms (anxiogenic profile). Acute administration of ipsapirone had no effect on any of the behavioural parameters at doses of 0.01 and 1 mg/kg IP, while 0.1 mg/kg IP produced a significant anxiogenic profile. Chronic treatment with ipsapirone (0.01, 0.1 and 1 mg/kg IP twice daily for 14 days) had no significant effect on rat behaviour on the X-maze but 24 h after ending treatment, ipsapirone at the highest dose used (1 mg/kg) produced a significant anxiogenic profile which was absent when the animals were tested 7 days after cessation of treatment. Ritanserin (0.05 and 0.25 mg/kg IP) had no effect acutely on any of the parameters measured but chronic treatment (0.25 mg/kg IP, twice daily for 14 days) produced a significant anxiolytic effect which was still present 24 h but not 7 days after cessation of treatment. Acute ondansetron (0.01, 0.1 and 1 mg/kg IP) had no effect while chronic ondansetron (0.01 mg/kg IP, twice daily for 14 days) produced a significant anxiolytic profile which was not a result of handling during the chronic dosing schedule, an effect was not measureable 24 h after treatment ended. The results demonstrate that the X-maze can detect anxiolytic activity in non-benzodiazepine drugs, as ritanserin and ondansetron showed anxiolytic profiles but only after chronic treatment. In contrast, the X-maze failed to detect any anxiolytic activity with the 5-HT1A partial agonist ipsapirone after either acute or chronic treatment.

Adrenergic alpha-Antagonists↗

PubMed1992

Attenuation of chemically induced defence response by 5-HT1 receptor agonists administered into the periaqueductal gray.

The ability of 5-HT1 receptor agonists to modulate a chemically induced defence response has been studied in Lister hooded rats. Microinjections of the excitatory amino acid D,L-homocysteic acid (DLH) in both rostral and caudal dorsal periaqueductal gray matter (PAG) caused explosive motor behaviour characteristic of defence. This behaviour was quantified in terms of response duration, arena revolutions and number of defensive jumps. Direct administration into the PAG of either 5-carboxamidotryptamine (5-CT) or 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) produced behaviours (decreased exploratory rearing, dose related onset of flat body posture) indicative of 5-HT1A receptor activation. Pretreatment with either 5-CT or 8-OHDPAT directly in the PAG caused a significant attenuation, and in some cases a complete abolition, of the DLH evoked response. These agonists share high affinity in vitro for the 5-HT1A receptor. Thus the results suggest that in vivo activation of 5-HT1A receptors mediates an antiaversive response with respect to defensive behaviour elicited by specific chemical stimulation of the dorsal PAG.

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

PubMed1992

Effect of established and putative anxiolytics on extracellular 5-HT and 5-HIAA in the ventral hippocampus of rats during behaviour on the elevated X-maze.

One of the proposed mechanisms of action for the anxiolytic effects of the benzodiazepines is via a decrease in central serotonergic neurotransmission. The aim of this study was to combine in vivo microdialysis in the rat with behaviour on the elevated X-maze to determine changes in 5-HT release in the ventral hippocampus with concomitant measurement of behaviour. Twenty minutes exposure to the elevated X-maze resulted in an increase in extracellular 5-HT in the ventral hippocampus with no change in extracellular 5-HIAA. Restricting the rat to either the open or the closed arms produced an increase in extracellular 5-HT, however the increase in 5-HT when restricted to the open arms was not significantly greater than that on the closed arms. Forty minutes pretreatment with diazepam (2.5 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus and had an anxiolytic profile over 5 min and 20 min exposures of the rats to the X-maze. Diazepam had no effect on basal 5-HT levels before exposure to the X-maze but reduced extracellular 5-HT levels when the animal was returned to the holding cage. Forty minutes pretreatment with the .5-HT1A receptor partial agonist ipsapirone (1 mg kg-1 IP) significantly inhibited the increase in extracellular 5-HT in the ventral hippocampus but did not produce behaviour different from vehicle controls after 5 or 20 min periods on the X-maze.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1992

Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry.

This series of experiments compared isolation-reared and socially reared rats for their locomotor activity, behavioural stereotypy, and monoamine function both postmortem and in vivo using intracerebral dialysis. In Experiment 1, isolates showed an altered time course of locomotor activity following d-amphetamine sulphate (AMPH) administration (0.5, 2.0, 3.0, or 5.0 mg/kg, SC). Isolation-reared rats also showed increased sensitivity to the sedative effects of a low dose of apomorphine hydrochloride (0.1 mg/kg) but did not differ from social controls following higher doses of the drug (0.5, 1.5, or 3.0 mg/kg, SC). Isolates showed a decrease in the intensity of apomorphine-induced stereotyped behaviours but no change in stereotypy induced by AMPH. In Experiment 2, isolates had higher postmortem dopamine (DA) concentrations and an altered asymmetry in DA function in the medial prefrontal cortex (PFC) but not in the nucleus accumbens (NAC) or caudate putamen (CPu). Isolated rats also had a lower 5-hydroxyindoleacetic acid (5-HIAA)/5-hydroxytryptamine (5-HT) ratio in the NAC (but not in the PFC or CPu) compared to controls. Experiment 3 used intracerebral dialysis to examine monoamine function in vivo following isolation rearing. Isolates showed greater increases in extracellular DA and greater decreases in DOPAC in response to 2 mg/kg AMPH SC in both the NAC and CPu. There were no apparent differences in the perfusate concentrations of either dopamine (DA), dihydroxyphenylacetic acid (DOPAC), or homovanillic acid (HVA) prior to drug administration. However, consistent with the results of Experiment 2, isolates had a reduced basal perfusate concentration of 5-HIAA from the NAC but not from the CPu. Experiment 4 measured postsynaptic DA function in CPu tissue slices following isolation. Isolation rearing did not affect cAMP accumulation in response to stimulation of D1 DA receptors by DA (0, 2.7, 9, or 30 microM). In addition, isolation rearing did not affect the coupling between D1 and D2 receptors, as measured by the increase in cAMP accumulation with 1 microM 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1 H-3-benzazepin (SK&F 38393) and its reduction by 10 microM quinperole hydrochloride (LY 171555). These results are discussed in terms of the possible relationship between these neurochemical findings and the behavioural disturbances following isolation rearing of rats.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Muscarinic antagonists attenuate neurotensin-stimulated accumbens and striatal dopamine metabolism.

The effect of scopolamine and atropine upon the increase in extracellular 3,4-dihydroxyphenylacetic acid induced by central injection of neurotensin was examined in the nucleus accumbens and the striatum of anaesthetized rats using in vivo differential pulse voltammetry with carbon fibre electrodes. Scopolamine (1 and 3 mg/kg, i.p.) and atropine (20 micrograms, i.c.v.) did not alter the 3,4-dihydroxyphenylacetic acid level in the nucleus accumbens or the striatum, measured for 60 min after administration. Neurotensin (10 micrograms, i.c.v.) increased the 3,4-dihydroxyphenylacetic acid peak height in both regions. Pretreatment with scopolamine (1 mg/kg) 15 min before neurotensin injection blocked the increase in extracellular 3,4-dihydroxyphenylacetic acid in the striatum but not in the nucleus accumbens whilst scopolamine (3 mg/kg) partially attenuated the effect of neurotensin in the nucleus accumbens and blocked the increase in 3,4-dihydroxyphenylacetic acid in the striatum. Atropine partially attenuated the effect produced by neurotensin in the nucleus accumbens and blocked the increase in 3,4-dihydroxyphenylacetic acid induced by the peptide in the striatum. However, the increase in extracellular 3,4-dihydroxyphenylacetic acid induced by haloperidol (1 mg/kg, s.c.) was not altered by scopolamine (1 mg/kg) or atropine. Also, the increase in dopamine metabolism in the nucleus accumbens and the striatum after centrally injected haloperidol (10 micrograms, i.c.v.) was not altered by atropine (20 micrograms, i.c.v.). Together, the results demonstrate a functional interaction between muscarinic antagonists and neurotensin on in vivo dopamine metabolism in the nucleus accumbens and the striatum but with a greater effect in the latter region.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Terminal autoreceptor control of 5-hydroxytryptamine release as measured by in vivo microdialysis in the conscious guinea-pig.

In vivo microdialysis in the frontal cortex of the freely moving guinea-pig was used to measure extracellular 5-hydroxytryptamine (5-HT) and study terminal autoreceptor control of its release. The indoleamine levels were determined by HPLC with electrochemical detection. Release of extracellular 5-HT and, to a lesser extent, 5-hydroxyindoleacetic acid was sensitive to tetrodotoxin, confirming the neuronal origin of measured neurotransmitter levels. Both systemic and local administration of the 5-HT1 agonist 5-carboxamidotryptamine caused inhibition of extracellular 5-HT levels, confirming the regulatory role of the terminal, and possibly also the somatodendritic, 5-HT autoreceptor on neuronal 5-HT release. Levels of extracellular 5-hydroxyindoleacetic acid were not affected by 5-carboxamidotryptamine following either central or peripheral administration.

Animals↗

PubMed1991

Effects of repeated treatment with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on the autoregulatory control of dorsal raphe 5-HT neuronal firing and cortical 5-HT release.

These experiments were designed to examine the effects of repeated 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) treatment on the autoregulatory control of cortical 5-HT release and dorsal raphe nucleus (DRN) 5-HT neuronal cell firing. Repeated DOI treatment decreased the behavioural responsiveness (wet-dog shakes) of 5-HT2 receptors and attenuated the inhibitory effects of the 5-HT1A receptor agonist, 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin), on both cortical 5-HT release and DRN 5-HT neuronal firing. In contrast, the inhibitory effect of acute DOI on cortical 5-HT release and DRN 5-HT neuronal firing was unaffected by repeated DOI treatment. The results demonstrate that changes in the responsiveness of 5-HT2 receptor function may influence the responsiveness of presynaptic 5-HT1A receptors regulating 5-HT neuronal function. The results also provide further evidence that the inhibition of cortical 5-HT release and DRN 5-HT neuronal firing produced by DOI is not mediated by 5-HT2 receptor activation.

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

PubMed1991

Inhibition of 5-hydroxytryptamine neuronal activity by the 5-HT agonist, DOI.

Systemic, intra-raphe and microiontophoretic administration of the 5-hydroxytryptamine (5-HT)1C/5-HT2 agonist (1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) inhibited the firing of 5-HT neurones in the dorsal raphe. DOI administered systemically and directly into the raphe also decreased the extracellular concentration of 5-hydroxytryptamine (5-HT) in the frontal cortex. In contrast, the administration of DOI directly into the frontal cortex did not significantly alter the concentration of frontal cortical extracellular 5-HT. The reduction of the firing rate of 5-HT neurons in the dorsal raphe and extracellular 5-HT concentration in the frontal cortex induced by systemic administration of DOI could not be blocked by the 5-HT2 antagonist ketanserin, ritanserin (5-HT2/5-HT1C antagonist) or the putative 5-HT1A antagonist, pindolol. These results suggest that the inhibition of 5-HT neuronal firing seen with administration of DOI is mediated via an action within the dorsal raphe and at least in close proximity to the 5-HT neurone cell bodies. The decrease in frontal cortical extracellular concentration of 5-HT release was not due to a direct action in the frontal cortex itself and may possibly be as a result of the decrease in the firing rate of the 5-HT neurones in the dorsal raphe. The mechanism of action of DOI to produce these effects is, however, unclear and warrants further investigation.

Amphetamines↗

PubMed1991

Behavioural rigidity and rule-learning deficits following isolation-rearing in the rat: neurochemical correlates.

Isolation-reared rats were compared to those reared in social groups on the acquisition of a conditional visual discrimination (Expt. I), a simultaneous (simple) light/dark discrimination and serial reversal learning (Expt. II). In Expt. I, rats reared in social isolation made more errors during the acquisition of the conditional discrimination but did reach a level of accurate performance which was comparable with that of socially-reared rats. Discrimination performance in isolates was less disruptable by manipulations of the task requirements. Reducing the number of stimulus lights or the introduction of a distracting stimulus increased the number of errors committed by socially-reared rats but did not significantly affect accuracy in isolates. Performance in isolated rats was also remarkably resistant to changes in motivational variables. Isolates responded more frequently during conditions of extinction and were virtually unaffected by pre-feeding prior to testing. In Expt. II, isolation-reared rats were not impaired in the acquisition of a simultaneous discrimination but unlike socially-reared rats isolates failed to show improvement with successive reversals of this discrimination. Isolates exhibited stronger position habits than socially-reared rats following reversal of the contingencies. These results of these two experiments combined have demonstrated a specific impairment in rule learning in isolates. Isolated rats were not impaired on a simultaneous discrimination in which accurate performance can be achieved simply by approaching the stimulus associated with reinforcement, but performed worse than controls on both the conditional discrimination and on serial reversal learning, another form of conditional task. In both of these latter tasks each stimulus becomes equally associated with reward and therefore performance can be improved by learning a rule. Post-mortem neurochemical measurements made at the completion of Expt. II revealed selective alterations in dopaminergic, serotoninergic and cholinergic markers in isolated rats. Correlational analyses indicated specific relationships between neurochemical and behavioural measurements.

Animals↗

PubMed1991

Use of amfonelic acid to discriminate between classical and atypical neuroleptics and neurotensin: an in vivo voltammetric study.

Previous ex vivo studies have shown that the non-amphetamine stimulant amfonelic acid potentiates the increase in DOPAC induced by classical but not by atypical neuroleptics. In the present study, we have demonstrated that this neurochemical model can be used to discriminate typical from atypical neuroleptics in vivo using differential pulse voltammetry with carbon fibre electrodes. The study also compared the effect of intracerebroventricular (i.c.v.) administration of neurotensin, on extracellular striatal DOPAC following amfonelic acid, with the effects of both classical and atypical neuroleptics. Saline or amfonelic acid (2.5 mg/kg s.c.) were administered; followed 5 min later by the classical neuroleptics haloperidol, perphenazine, or the atypical neuroleptics clozapine, thioridazine, or by neurotensin. After drug administration extracellular striatal DOPAC was recorded every 5 min for 90 min. Amfonelic acid did not alter basal striatal DOPAC but potentiated the increase in DOPAC induced by haloperidol (1.0 and 0.05 mg/kg s.c.) and perphenazine (10 mg/kg s.c.). Both clozapine (30 mg/kg i.p.) and thioridazine (20 mg/kg s.c.) increased extracellular DOPAC, but pretreatment with amfonelic acid prevented the increase in DOPAC produced by both drugs. Neurotensin (10 micrograms, i.c.v.), in a similar manner to the atypical neuroleptics, increased extracellular DOPAC in the striatum and the effect was prevented by amfonelic acid. The present study demonstrates that pretreatment with amfonelic acid is a valuable tool to discriminate between classical and atypical neuroleptics in vivo. The results also indicate that neurotensin in the presence of amfonelic acid has a profile similar to the atypical neuroleptics.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Effects of idazoxan on dorsal raphe 5-hydroxytryptamine neuronal function.

The effects of the alpha 2-adrenoceptor antagonist idazoxan on 5-hydroxytryptamine (5-HT) neuronal firing and release have been investigated. Idazoxan, administered i.v. (10 micrograms/kg and 0.5 mg/kg) increased dorsal raphe nucleus (DRN)-5-HT neuronal firing rate in a dose-dependent fashion. At the higher dose, a voltammetric study revealed increases in extracellular 5-HT and 5-hydroxyindole acetic acid (5-HIAA) levels, there was no effect with the lower dose. Intra-raphe administration of idazoxan (1 ng) also elevated the firing rate of 5-HT neurones in the dorsal raphe, suggesting that idazoxan may produce the increase in firing by a direct effect in the DRN. However, microiontophoretic application of idazoxan did not increase the firing rate of 5-HT neurones in the DRN. Thus the increase in the firing rate of 5-HT neurones in the DRN observed with systemic and local administration of idazoxan is probably not due to a direct action of idazoxan on the 5-HT neurone. Possibly the idazoxan acted at alpha 2-adrenoceptors located on noradrenergic terminals thus stimulating noradrenaline release and consequently increased 5-HT activity. Chronic administration of idazoxan (0.8 mg/kg per h for 14 days), using osmotic mini-pumps, caused an elevation in basal firing rate and an attenuation of the inhibitory response of DRN 5-HT neurones to the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OHDPAT) (10 micrograms/kg i.v.). This finding suggests that chronic infusion with idazoxan leads to desensitisation of the 5-HT1A somatodendritic autoreceptor.

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

PubMed1991

Effect of isolation rearing on 5-HT agonist-induced responses in the rat.

Rats were reared from weaning (21 days of age) either in isolation or in social groups of five for 30 days and were then tested for spontaneous locomotor activity and 7 days later for 5-hydroxytryptamine (5-HT) agonist-induced behaviour. Isolation-reared animals displayed locomotor hyperactivity when placed in a novel environment. 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (2 mg/kg IP) and 8-hydroxy-2-(di-n-propyl-amino) tetralin (8-OH-DPAT) (0.32 mg/kg SC) elicited various components of the "5-HT behavioural syndrome" in both groups of animals, with forepaw treading and flat body posture being significantly more pronounced in isolation-reared animals. 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (2.5 mg/kg IP), a 5-HT2 selective agonist, produced a significantly greater number of back muscle contractions in isolation-reared animals but there was no difference between the two groups in the number of wet-dog shakes produced. Forepaw treading and flat body posture are thought to be mediated by 5-HT1A receptor activation, and stimulation of this receptor by either 5-MeODMT or 8-OH-DPAT produced greater responding in isolation-reared rats, suggesting supersensitivity of the post-synaptic 5-HT1A receptor. Wet-dog shakes are thought to be mediated by 5-HT2 and other (none-5-HT) receptors while back muscle contractions have been shown to be mediated by 5-HT2 receptors, indicating that there is also an increase in 5-HT2 receptor responsiveness in the socially-isolated animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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