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Biomedical subjects

F S Radhakishun

Publications and source records attributed to F S Radhakishun.

11 recordsLinked to original sources
PubMed1994

Subchronic treatment with the neuroleptic-like peptide desenkephalin-gamma-endorphin may decrease dopaminergic neurotransmission in the nucleus accumbens of rats.

In rats, subchronic administration of desenkephalin-gamma-endorphin (DE gamma E) into the nucleus accumbens or subcutaneously for 10 days resulted in hypoactivity. Intra-accumbens administration caused a significant reduction in the nucleus accumbens tissue levels of the dopamine (DA) metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Systemic administration of DE gamma E decreased DOPAC and 5-hydroxyindoleacetic acid (5-HIAA) levels in nucleus accumbens tissue. Subchronic subcutaneous DE gamma E treatment reduced the basal release of [3H]DA from rat nucleus accumbens slices in vitro and the basal release of endogenous DA and DOPAC in vivo as assessed with on-line dialysis in the nucleus accumbens of freely moving rats. The DA agonist N,N-dipropyl-7-hydroxy-2-aminotetralin (DP-7-ATN) was equally effective in inhibiting [3H]DA release elicited by electrical stimulation from slices of subchronically DE gamma E and placebo treated rats. Administration of a small dose of apomorphine caused similar reductions of the in vivo release of DA and DOPAC in both placebo and DE gamma E treated rats. These results indicate that subchronic DE gamma E treatment may decrease dopaminergic neurotransmission in the nucleus accumbens. This effect is probably not due to alterations in the sensitivity of presynaptically located DA autoreceptors mediating DA release in vitro and in vivo.

Animals↗
PubMed1990

Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. I. Behavioral and biochemical studies.

Bilateral 6-hydroxydopamine (6-OHDA) lesions in the nucleus accumbens of rats induced motor hypoactivity 7 days after the lesion. Spontaneous functional recovery of this impaired behavior occurred in 3-4 weeks. Behavioral and biochemical studies suggest that the hypoactivity is due to damage of the dopamine systems in the nucleus accumbens. The 6-OHDA lesions induced a decrease in the nucleus accumbens levels of dopamine and its metabolites of about 30% both 7 and 20 days after the lesion. The in vitro uptake of [3H]dopamine in nucleus accumbens tissue of the 6-OHDA-lesioned rats was decreased to the same extent at 7, 14 and 28 days after the lesion. Scatchard analysis of [3H]haloperidol binding studies in nucleus accumbens tissue revealed a shift from one type of binding site in tissue of sham-lesioned rats to two types of binding sites in tissue of 6-OHDA-lesioned rats 29 days after the lesion. This shift was not present in nucleus accumbens tissue 8 days after a 6-OHDA lesion. The spontaneously recovered rats showed an enhanced behavioral response upon administration of the dopamine agonist apomorphine. The present data suggest that the spontaneous functional recovery of impaired motor activity is caused by the development of supersensitivity of the dopamine receptor systems in the nucleus accumbens. This supersensitivity may be the result of increased affinity of one type of binding site or an increased number of functional binding sites.

Animals↗
PubMed1990

Functional recovery after destruction of dopamine systems in the nucleus accumbens of rats. II. Facilitation by the ACTH-(4-9) analog ORG 2766.

Functional recovery from motor hypoactivity of rats with 6-OHDA lesions in the nucleus accumbens is accelerated by intra-accumbal or subcutaneous treatment with the ACTH-(4-9) analog ORG 2766. The spontaneous recovery period of 3 weeks is shortened to 7 days by daily treatment with this peptide during the first 6 days after the lesion. The 6-OHDA lesion induced a decrease of about 30-40% in the levels of dopamine, HVA and DOPAC as well as in the uptake of [3H]dopamine in nucleus accumbens tissue in vitro. Treatment with ORG 2766 during the first 6 days following the lesion did not affect the lesion-induced changes in these biochemical parameters. Binding studies with [3H]haloperidol in nucleus accumbens tissue of placebo or ORG 2766-treated sham-lesioned rats revealed a linear Scatchard plot 7 days after the sham lesion. In tissue of placebo-treated 6-OHDA lesioned animals a similar linear Scatchard plot was found but in tissue of ORG 2766-treated 6-OHDA-lesioned rats the Scatchard plot was curvilinear in shape indicating two types of binding sites. In the 6-OHDA-lesioned rats treated with ORG 2766 the behavioral response upon apomorphine challenge was enhanced suggesting the existence of functional supersensitivity of the DA system. Similar changes in Scatchard plots and apomorphine-induced behavioral changes have been previously reported after spontaneous recovery. The present study indicates that ORG 2766 accelerates the process of functional recovery from impaired motor behavior of rats with 6-OHDA lesions in the nucleus accumbens, which may be due to development of denervation supersensitivity.

Adrenocorticotropic Hormone↗
PubMed1988

Dopamine release in the nucleus accumbens of freely moving rats determined by on-line dialysis: effects of apomorphine and the neuroleptic-like peptide desenkephalin-gamma-endorphin.

This study examined the effects of apomorphine, sulpiride, desenkephalin-gamma-endorphin (DE gamma E) and a combination of DE gamma E with apomorphine on the release of dopamine (DA) and its main metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the nucleus accumbens of freely moving rats. A fully automated on-line brain dialysis system was used. A small dose of s.c. administered apomorphine induced a decrease in the output of DA and DOPAC. Sulpiride, infused into the nucleus accumbens, induced a 2-fold increase in the output of DA, DOPAC and HVA. DE gamma E hardly modified either the basal release of DA, DOPAC and HVA or the apomorphine-induced attenuation of the release of DA and DOPAC. These results indicate a dissociation between the behavioural effects of DE gamma E and its effect on the release of DA in vivo.

Animals↗
PubMed1988

Scheduled eating increases dopamine release in the nucleus accumbens of food-deprived rats as assessed with on-line brain dialysis.

This study examined the effect of scheduled eating on the in vivo release of dopamine (DA) in the nucleus accumbens of rats that were maintained on a food deprivation schedule. DA release was measured by means of a fully automated on-line brain dialysis system. The initiation of eating increased the release of DA, which remained elevated during the entire eating period. Termination of eating caused a gradual decrease of the release of DA to basal values. Increased motor activities did not change the release of DA. These results indicate a link between eating and DA release and demonstrate the suitability of on-line brain dialysis for behavioural experiments.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Desenkephalin-gamma-endorphin and neuroleptics counteract the DP-7-ATN-induced hypomotility after intra-accumbens treatment.

Injection of the selective presynaptic dopamine agonist N,N-dipropyl-7-hydroxy-2-aminotetralin (DP-7-ATN, 1 fg to 1 microgram) into the nucleus accumbens decreased motor activity. The reduction of motor activity was reversed by pretreatment with haloperidol (10 pg), (-)-sulpiride (10 pg) or desenkephalin-gamma-endorphin (DE gamma E) (100 pg). These results support the hypothesis that DE gamma E may interfere with presynaptically located D-2 dopamine receptor systems in the nucleus accumbens. Furthermore, the use of DP-7-ATN in the described test procedure might be a useful model for testing novel neuroleptic compounds in vivo.

Animals↗
PubMed1988

The response of apomorphine administered into the accumbens in rats with bilateral lesions of the nucleus accumbens, induced with 6-hydroxydopamine.

Bilateral lesions of the nucleus accumbens, induced with 6-hydroxydopamine, reduced motor activity and produced a 20-35% depletion of the concentrations of dopamine (DA) and its main metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Small doses of apomorphine (1-10 ng), injected into the nucleus accumbens of sham-lesioned rats, decreased motor activity, while larger doses (1-10 micrograms) produced hyperactivity. In rats lesioned with 6-hydroxydopamine, apomorphine caused hyperactivity only, and this apomorphine-induced response was more pronounced than in sham-lesioned rats. Large doses of apomorphine decreased, only in sham-lesioned animals, the levels of DOPAC and HVA. These data suggest that the apomorphine-induced hypomotility is mediated by presynaptically located DA receptor systems in the nucleus accumbens, whereas the apomorphine-induced hypermotility is likely to be mediated by postsynaptically located DA receptor systems.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1987

The neuroleptic-like peptide desenkephalin-gamma-endorphin does not antagonize the dopamine receptor agonist-induced inhibition of the release of [3H]dopamine from rat nucleus accumbens slices in vitro.

In rats, the non-opioid beta-endorphin (beta E) fragment desenkephalin-gamma-endorphin (DE gamma E, beta E6-17) antagonizes the hypomotility induced by a small dose of dopamine (DA) receptor agonists. It has been suggested that DE gamma E might act in this respect by a direct or indirect blockade of presynaptically located DA receptors in the nucleus accumbens, thereby causing an increase of DA release. Therefore in the present study the effect of DE gamma E was examined on DA receptor agonist-induced inhibition of the electrically evoked release of previously accumulated [3H]DA from rat nucleus accumbens slices in vitro. The DA receptor agonists apomorphine, LY 171555 and n,n-di-n-propyl-7-hydroxy-2-aminotetralin (DP-7-AT) inhibited in a concentration-dependent manner the electrically evoked release of [3H]DA. The selective D2 receptor antagonist (-)-sulpiride blocked the effects of apomorphine, corroborating that the DA receptor involved is of a D2 type. DE gamma E was tested at several concentrations (10(-9)-10(-6) M) and under various experimental conditions. DE gamma E, by itself, did not affect either the electrically stimulated or the basal release of [3H]DA. The inhibiting effect of DA receptor agonists was slightly reduced by DE gamma E, but this effect was present in some experiments only. It is concluded that DE gamma E does not function as an antagonist for the DA receptor mediating DA release and that the interaction observed in behavioural experiments between DA agonists and DE gamma E does not occur at the level of this receptor.

Animals↗
PubMed1987

The hypomotility elicited by small doses of apomorphine seems exclusively mediated by dopaminergic systems in the nucleus accumbens.

The reduction of motor activity elicited in rats by a subcutaneous injection of a small dose of apomorphine was reversed by pretreatment of the nucleus accumbens with haloperidol (10 pg), sulpiride (10 pg) or desenkephalin-gamma-endorphin (DE gamma E) (100 pg or 10 ng). These doses of the compounds did not change motor activity in placebo-treated rats. Pretreatment of the nucleus caudatus with the same neuroleptics or DE gamma E did not diminish the effect of subcutaneously administered low doses of apomorphine. A small dose of apomorphine decreased motor activity when it was injected directly into the nucleus accumbens. This effect was dose dependently antagonized by subcutaneous pretreatment with DE gamma E. It is suggested that the hypoactivity elicited by small doses of apomorphine is exclusively mediated by dopaminergic systems in the nucleus accumbens.

Analysis of Variance↗
PubMed1983

The release of endogenous dopamine and its metabolites from rat striatum as detected in push-pull perfusates: effects of systematically administered drugs.

The release of dopamine (DA) and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was determined in push-pull perfusates from the striatum of the anaesthetized rat with high pressure liquid chromatography and electrochemical detection. Striking differences were found between the released amounts of DA (less than 7 fmol/min) and those of the metabolites (approx 0.5 pmol/min). It was calculated that 5% of the DA metabolites left the striatum via the push-pull cannula. The effects of systemic application of apomorphine, (+)-amphetamine, haloperidol or haloperidol in combination with amfonelic acid on the release of DA and its metabolites, were investigated. The release rate of DOPAC correlated well with the drug-induced changes of these metabolites in striatal tissue, however, this was not the case for HVA. The increase of striatal levels of DOPAC and HVA induced by the anaesthesia is a serious limitation of the method. To enable reliable estimation of the release of DA, 1 microM (+)-amphetamine had to be added to the perfusion medium (which may have modified the origin of DOPAC and HVA in the perfusates). (+)-Amphetamine (5 mg/kg, intravenous) induced a two- to threefold increase in the release of DA. Systemic administration of apomorphine, haloperidol or haloperidol in combination with amfonelic acid did not change the output of the neurotransmitter in the push-pull cannula. This implies that neuroleptics cause only a small and transient rise in DA release, whereas the pronounced and persisting increase in DOPAC and HVA seen after neuroleptics is the result of enhanced metabolism related to increased synthesis of DA.

3,4-Dihydroxyphenylacetic Acid↗