1,721,053 research outputs found
Ethanol preferentially stimulates dopamine release in the nucleus accumbens of freely moving rats.
No full textPreferential stimulation of dopamine release in the nucleus accumbens by opiates, alcohol, and barbiturates: studies with transcerebral dialysis in freely moving rats.
No full textRapid tolerance to neuroleptic-induced stimulation of dopamine release in freely moving rats.
No full textThe effect of repeated s.c. administration of various neuroleptics (haloperidol, sulpiride and cis-flupentixol) on the in vivo release and metabolism of dopamine (DA) was studied in freely moving rats using trans striatal dialysis coupled to reverse-phase high-pressure liquid chromatography with electrochemical detection. Acute administration of neuroleptics dose-dependently but transiently stimulates DA release whereas lastingly stimulating DA metabolism. Administration of a second dose of neuroleptic, 4 to 12 hr after a priming dose, fails to stimulate DA release or stimulates it less effectively than in normal rats. A normal stimulatory response of DA release is reinstated when at least a 24-hr delay between the two doses is allowed. In contrast, the ability of the second neuroleptic dose to affect DA metabolism is unchanged. The results indicate that rapid tolerance takes place to neuroleptic-induced stimulation of DA release but not of DA metabolism
Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.
No full textThe effect of various drugs on the extracellular concentration of dopamine in two terminal dopaminergic areas, the nucleus accumbens septi (a limbic area) and the dorsal caudate nucleus (a subcortical motor area), was studied in freely moving rats by using brain dialysis. Drugs abused by humans (e.g., opiates, ethanol, nicotine, amphetamine, and cocaine) increased extracellular dopamine concentrations in both areas, but especially in the accumbens, and elicited hypermotility at low doses. On the other hand, drugs with aversive properties (e.g., agonists of kappa opioid receptors, U-50,488, tifluadom, and bremazocine) reduced dopamine release in the accumbens and in the caudate and elicited hypomotility. Haloperidol, a neuroleptic drug, increased extracellular dopamine concentrations, but this effect was not preferential for the accumbens and was associated with hypomotility and sedation. Drugs not abused by humans [e.g., imipramine (an antidepressant), atropine (an antimuscarinic drug), and diphenhydramine (an antihistamine)] failed to modify synaptic dopamine concentrations. These results provide biochemical evidence for the hypothesis that stimulation of dopamine transmission in the limbic system might be a fundamental property of drugs that are abused
CY 208-243, a novel dopamine D-1 receptor agonist, fails to modify dopamine release in freely moving rats.
No full textCY 208-243, a novel D-1 agonist structurally unrelated to other D-1 agonists, at doses which elicited behavioural stimulation with locomotion, sniffing and grooming, failed to modify the release and metabolism of dopamine (DA) in the nucleus accumbens and in the dorsal caudate of freely moving rats, as estimated by transcerebral dialysis. CY 208-243 prevented the increase of DA release and metabolism elicited by the specific D-1 antagonist, SCH 23390, but not by the specific D-2 antagonist, sulpiride. The results support the conclusion that CY 208-243 is an effective and specific D-1 agonist in vivo
Effects of locally applied D-1 and D-2 receptor agonists and antagonists studied with brain dialysis.
No full textThe effect on dopamine (DA) release of D-1 and D-2 receptor agonists and antagonists applied locally in the caudate through a trans-striatal dialysis probe was studied in freely moving rats. D-2 agonists (LY 171555 and BHT 920) reduced DA release in a concentration-dependent manner. The same local application of haloperidol abolished the effect of 10 microM LY 171555 and BHT 920. A specific D-1 agonist, the catechol benzazepine SKF 38393, reduced DA release and this effect was not modified by systemic or local administration of the D-1 antagonist, SCH 23390, nor by the D-2 antagonist, haloperidol. In contrast, the non-catechol D-1 agonist, CY 208243, failed to modify DA release. Local application of the D-1 antagonist, SCH 23390, or of the D-2 antagonist, (-)-sulpiride, stimulated DA release in a concentration-dependent manner. The D-1 agonist, CY 20843, reversed the stimulatory effect of SCH 23390 but not that of (-)-sulpiride. It is concluded that D-1 and D-2 receptors located in the caudate control DA release separately in this area
Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.
No full textWe studied the effect of opiates acting preferentially on mu receptors, like morphine, methadone and fentanyl (mu agonists) and on kappa receptors, like U50,488, bremazocine and tifluadom (kappa agonists) on the release of dopamine (DA) and of its metabolites, dihydroxyphenylacetic acid and homovanillic acid, from the nucleus accumbens and from the dorsal caudate of freely moving rats using brain dialysis coupled to high-performance liquid chromatography with electrochemical detection. Spontaneous behavior was videotaped and analyzed by estimating the percentage of time spent by the animals in performing certain specific behavioral items. Mu agonists stimulated DA-release and metabolism in the accumbens at lower doses than in the caudate. Maximal stimulation of DA release did not exceed 100% except after high doses of methadone (10 mg/kg) which stimulated DA release in the accumbens by more than 300%, possibly as a result of hypoxia. Stimulation of DA release was associated to stimulation of behavior at low doses and to a biphasic inhibitory-stimulatory syndrome after higher doses of the opiates. Pretreatment with low doses of naloxone (0.1 mg/kg s.c.) or with the irreversible mu antagonist beta-funaltrexamine (10 nmol i.c.v.) increased the ED50 for the stimulation of DA release by the three opiates. In contrast with mu agonists, agonists of kappa receptors like U50,488, bremazocine and tifluadom decreased DA release in the accumbens and in the caudate and reduced motor activity. These effects were antagonized only by rather high doses of naloxone (2.5 mg/kg s.c.) and were not affected by pretreatment with beta-funaltrexamine (10 nmol i.c.v.).(ABSTRACT TRUNCATED AT 250 WORDS
Preferential stimulation of dopamine release in the nucleus accumbens of freely moving rats by ethanol.
No full textThe effect of the i.p. administration of ethanol on the release of dopamine (DA) and on the output of its main metabolites, dihydroxyphenylacetic acid and homovanillic acid, was estimated in the rat by transcerebral dialysis of two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of ethanol (0.25-0.5 g/kg i.p.) stimulated DA release specifically in the n. accumbens and elicited pure behavioral stimulation. Higher doses of ethanol (1.0-2.5 g/kg) elicited sedation and hypnosis and stimulated further DA release and dihydroxyphenylacetic acid and homovanillic acid output in the accumbens and, although less, also in the caudate. High doses of ethanol (5 g/kg i.p.) elicited long-lasting hypnosis and sedation and induced a depression followed by stimulation of DA release in the accumbens. DA release in the caudate was stimulated further. Low doses of apomorphine (0.05 mg/kg s.c.) reversed completely the stimulant effect of 0.5 g/kg of ethanol on behavior and on DA release in the accumbens. Moreover, the stimulation of behavior and of DA release in the accumbens elicited by 0.5 g/kg of ethanol were abolished completely by pretreatment with 700 mg/kg of gamma-butyrolactone, an agent which blocks DA firing and DA release. The results indicate that ethanol preferentially stimulates DA transmission in the mesolimbic system probably by activating the firing activity of mesolimbic DA neurons and provide direct evidence that these changes are involved in the motor stimulant effects of ethanol
Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection: a new method for the study of the in vivo release of endogenous dopamine and metabolites.
No full textA method for the estimation in rats of the in vivo release and metabolism of dopamine (DA) is described. The method is based on the dialysis principle and consists of inserting transversally in the striatum a thin (0.2 mm) dialysis tube (Amicon Vitafiber) which is then perfused with Ringer. The Ringer, flowing at a constant rate of 2 microliters/min in the dialysis tube, extracts low molecular weight substances from the surrounding tissue by way of simple diffusion along a concentration gradient. At the distal end of the dialysis tube, the Ringer is collected every 10 to 20 min and directly injected into a high performance liquid chromatographer (HPLC) equipped with reverse phase octadecyl sulfate columns which separate DA and its metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). These substances are then quantitatively estimated by oxidative electrochemical detection. The basal output of DA is 0.3 pmol/20 min, whereas the outputs of DOPAC and HVA are 60 and 20 pmol/20 min, respectively. In basal conditions the output of DA, DOPAC, and HVA is stable over at least 10 hr. Histological examination of the track left by the dialysis probe in rats after 10 hr of continuous dialysis reveals very little damage and normal neuronal morphology in the vicinity of the dialysis tube. Increase of the K+ concentration in the Ringer to 30 mM produced a sharp, reversible increase of DA output. Both the basal and K+-stimulated release were Ca++ dependent, because omission of Ca++ abolished basal and K+-stimulated DA release. Electrical stimulation of the nigrostriatal DA neurons in the medial forebrain bundle sharply increased DA output. Amphetamine sulfate in low doses (1.0 mg/kg, i.v.) produced a 9-fold increase in DA release and decreased DOPAC and HVA output. alpha-Methyl tyrosine (150 mg/kg, i.v.) reduced within 2 hr DA release to 15% of basal values and in parallel also decreased the output of DOPAC and HVA. Reserpine (5 mg/kg, i.p.) reduced DA release but in a slower fashion than alpha-methyl tyrosine and increased DOPAC and HVA. Pargyline (75 mg/kg, i.p.) produced a 4-fold increase of DA release, while it rapidly brought to zero DOPAC and HVA output. gamma-Butyrolactone (700 mg/kg, i.p.) rapidly and lastingly reduced DA, DOPAC, and HVA output. The biochemical and histological results obtained indicate that the method is suitable to estimate in the rat the changes in the release o f endogenous DA and its metabolites which take place in vivo under administration of centrally acting drug
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