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A Imperato

Publications and source records attributed to A Imperato.

At least 73 records · Page 4Linked to original sources
PubMed1991

Changes in brain dopamine and acetylcholine release during and following stress are independent of the pituitary-adrenocortical axis.

Microdialysis was employed to assess extracellular dopamine from medial prefrontal cortex, nucleus accumbens, nucleus caudatus, and acetylcholine from the hippocampus of conscious rats during and after 120 min restraint stress. Restraint stress rapidly stimulated the release and the metabolism of dopamine in the medial prefrontal cortex and in the nucleus accumbens, and acetylcholine release in the hippocampus. Fifty-sixty min later, although rats were still restrained, dopamine and acetylcholine release gradually returned to basal levels. When the animals were freed a considerable increase in the release of both neurotransmitters was observed. No changes in the striatum were observed throughout the experiments. The time-course of plasma corticosterone did not parallel that of dopamine and acetylcholine release, increasing during the whole stress procedure, and decreasing when the animals were released. Adrenalectomized rats responded to stress and liberation in much the same way as intact rats. The administration of exogenous corticosterone (0.5-1.5 mg/kg s.c.) did not change the release of dopamine from the prefrontal cortex and nucleus accumbens, and of acetylcholine from the hippocampus, while the dose of 3.0 mg/kg which stimulated them, raised plasma corticosterone to very high concentrations which had never been attained during stress. Moreover, RU 38486, an antagonist of brain glucocorticoid receptors, did not antagonize the stress-induced increase of neurotransmitter release.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1991

In vivo probing of the brain cholinergic system in the aged rat. Effects of long-term treatment with acetyl-L-carnitine.

The regulation of acetylcholine (ACh) release by the different subtypes of muscarinic (M) receptors in the hippocampus of freely-moving Fischer and Sprague-Dawley rats, was investigated. Atropine (10 mumol/kg i.p.) induced a pronounced increase of ACh release (+400% over basal values) in the hippocampus of young rats (3 months) while the effect was drastically reduced (+100% over basal values) in old rats (24 months). The preferential M2 antagonist AF-DX 116 (50 mumol/kg i.p.) showed similar effects in young and old rats being, furthermore, 10 times less potent than atropine. The preferential M1 antagonist pirenzepine (50 mumol/kg i.p.) was even less potent than AF-DX 116 in enhancing ACh release in young rats, while the effect was more pronounced in the old ones. Therefore, the effect of the preferential M3 antagonist 4-DAMP was studied. 4-DAMP 10(-6) M, dissolved in the Ringer solution perfusing the hippocampus, induced an enhancement of ACh release (+200% and +70% over basal values, in young and old rats, respectively) which was comparable to that obtained after atropine at the same concentration. AF-DX 116 and pirenzepine, on the other hand, were by far less potent. Six months' pretreatment with acetyl-l-carnitine (ALCAR) reduced the significant differences between young and old rats in the release response after M1 and M3 receptor antagonists. Taken all together, these findings indicate that the regulation of ACh release, at least in the hippocampus, is mainly through the M3 receptors subtype of muscarinic receptors and that this subtype is the most involved in the aging process. Moreover, the ability of ALCAR to preserve the receptor-mediated functional ACh release response with respect to old animals suggests that ALCAR could be utilized in the amelioration of receptor functionality in the aging brain.

Acetylcarnitine↗
PubMed1990

Dopamine release in the nucleus caudatus and in the nucleus accumbens is under glutamatergic control through non-NMDA receptors: a study in freely-moving rats.

Perfusion with quisqualate (5 x 10(-6) M) and kainate (5 x 10(-7) M), selective agonists of glutamate receptors, enhanced the release of dopamine in both caudate and accumbens nuclei of freely-moving rats, measured by the transcerebral microdialysis technique. In contrast, N-methyl-D-aspartate (NMDA) did not affect dopamine release, except at very high concentrations (10(-2) M). The quisqualate-kainate antagonist, FG 9041 (DNQX), antagonized the elevation of dopamine release induced by quisqualate and, furthermore, reduced that of kainate. CPP, a selective NMDA antagonist, did not counteract the quisqualate- or kainate-induced stimulation of dopamine release. The enhancement of dopamine release after quisqualate and kainate was accompanied by behavioural stimulation characterized by grooming, rearing, hypermotility with sniffing and confined sniffing. This behavioural syndrome could be blocked by haloperidol. Conversely, perfusion with NMDA did not activate behaviour even at high concentrations. These results indicate that the dopaminergic system, within the caudate and the accumbens nuclei, is under glutamatergic control through kainate and quisqualate receptors, while the NMDA receptors do not appear to be involved.

Animals↗
PubMed1990

Stress activation of limbic and cortical dopamine release is prevented by ICS 205-930 but not by diazepam.

Systemic administration of the 5-HT3 receptor antagonist ICS 205-930, but not of the benzodiazepine diazepam, was able to prevent the stimulation of dopamine release in the nucleus accumbens and prefrontal cortex induced by restraint stress. These findings suggest that stress is not simply co-extensive with anxiety and that 5-HT3 receptors could regulate the dopaminergic response to stress.

Animals↗
PubMed1989

Acetyl-L-carnitine enhances acetylcholine release in the striatum and hippocampus of awake freely moving rats.

The effect of acetyl-L-carnitine (ALC) on the spontaneous release of acetylcholine (ACh) in the striatum and hippocampus of freely moving rats was investigated using brain microdialysis coupled with HPLC-electrochemical detection. Systemic administration of ALC, in a dose-dependent manner, stimulated ACh release in both areas, while the D-enantiomer was substantially ineffective. The effect of ALC was strongly Ca2+ dependent and tetrodotoxin (TTX) sensitive. These features of an exocytotic and impulse flow-dependent mechanism suggest that the increase in ACh release is the result of ALC activation of a physiological mechanism in cholinergic neurons.

Acetylcarnitine↗
PubMed1989

5-HT3 receptors control dopamine release in the nucleus accumbens of freely moving rats.

ICS 205-930, a selective and potent 5-HT3 receptor antagonist applied either systemically, or locally into the ventral tegmental area, antagonized the stimulation of dopamine release in the nucleus accumbens, induced by the subcutaneous administration of morphine. These findings, obtained by the use of brain microdialysis in awake freely-moving rats, demonstrate in vivo a functional role of 5-HT3 receptors in the brain. Since stimulation of dopamine release in the nucleus accumbens is a prerequisite for the expression of the rewarding properties of morphine, its suppression by ICS 205-930 suggests a possible application of 5-HT3 receptor antagonists in the treatment of addiction.

Animals↗
PubMed1989

CY 208-243, a novel dopamine D-1 receptor agonist, fails to modify dopamine release in freely moving rats.

CY 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.

Animals↗
PubMed1989

Biochemical and behavioural properties of clozapine.

The selection and early development of clozapine was based upon its gross behavioural, arousal-inhibiting, sleep-promoting, and caudate spindle-prolonging properties. Compared to classical neuroleptics, clozapine causes only a short-lasting elevation of plasma prolactin levels, elevates both striatal homovanillic acid and dopamine content, is devoid of marked apomorphine-inhibitory or cataleptogenic activity and fails to induce supersensitivity of striatal dopaminergic systems after chronic administration. Clozapine's intrinsic anticholinergic activity, while stronger than that of other neuroleptic agents, does not appear to underlie either its failure to induce tardive dyskinesias or its superior antipsychotic activity. Furthermore, the overlap between clozapine and several classical neuroleptics with regard to alpha-adrenergic-, serotonin- and histamine-blocking activity makes it unlikely that one or more of these properties is the key to its atypical characteristics. More recent findings show that clozapine and classical neuroleptics differ with regard to their indirect effects on nigral GABA-ergic mechanisms implicated in the induction of tardive dyskinesias and, possibly in keeping with this, that clozapine and similar agents exhibit preferential blockade of D-1 dopamine receptors in the whole animal. Such an action of clozapine in man could well explain both its low EPS liability and, in some subjects, its superior antipsychotic activity.

Animals↗
PubMed1989

Amphetamine, cocaine, phencyclidine and nomifensine increase extracellular dopamine concentrations preferentially in the nucleus accumbens of freely moving rats.

The effect of systemically administered amphetamine, cocaine, phencyclidine and nomifensine on the extracellular concentrations of dopamine in freely moving rats was estimated by microdialysis in the nucleus accumbens and in the dorsal caudate. All the drugs tested stimulated dopamine output in both areas but more effectively in the accumbens as compared to the caudate. Low doses of cocaine (1.0 mg/kg s.c.) stimulated dopamine output only in the nucleus accumbens. Nomifensine (1.25-5.0 mg/kg s.c.) increased by a similar extent peak dopamine output in the two dopaminergic areas but the duration of the effect was longer in the accumbens as compared to the caudate. The effect of cocaine, phencyclidine and nomifensine was prevented by systemic gamma-butyrolactone (700 mg/kg i.p.) and by omitting Ca2+ from the Ringer used for dialysis, the effect of amphetamine was insensitive to these manipulations. Thus, in contrast with amphetamine, cocaine, phencyclidine and nomifensine increase synaptic dopamine concentrations in vivo by a mechanism which depends on intact activity of dopaminergic neurons and by an exocytotic process.

Amphetamines↗
PubMed1989

The effects of clozapine and fluperlapine on the in vivo release and metabolism of dopamine in the striatum and in the prefrontal cortex of freely moving rats.

The effects of the two atypical neuroleptics clozapine and fluperlapine on the dopaminergic function in the striatum and in the prefrontal cortex were studied using the transversal microdialysis technique in awake, freely moving rats. Although neither drug induced catalepsy in rats, both increased the release of dopamine (DA) and the output of its metabolites in a similar way in both areas. Unlike classical neuroleptics, after clozapine and fluperlapine administration, the stimulation of DA release was strictly coupled to that of the metabolites, and a second injection was able to renew it. Pretreatment with the selective D1 agonists SKF 38393 or CY 208-243, by themselves ineffective on the release of DA, antagonized the effects of low doses and substantially reduced those of higher doses of clozapine and fluperlapine, indicating that these two atypical drugs act, depending on the dose, selectively or partially through D1 receptors.

Animals↗
PubMed1988

Effects of locally applied D-1 and D-2 receptor agonists and antagonists studied with brain dialysis.

The 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.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1988

Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats.

The 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.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.

We 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)

Animals↗
PubMed1988

Pharmacological profile of dopamine receptor agonists as studied by brain dialysis in behaving rats.

Using the technique of brain dialysis in freely moving rats we have investigated the effect of various dopamine (DA) receptor agonists on the release and metabolism of DA in two terminal dopaminergic areas, the nucleus accumbens and the dorsal caudate. Low doses of various DA receptor agonists such as apomorphine (12-100 micrograms/kg s.c.), LY 171555 (5-50 micrograms/kg s.c.), pergolide (5-25 micrograms/kg s.c.), (+)-3PPP (0.5-2.5 mg/kg s.c.) and BHT 920 (10-250 micrograms/kg s.c.) reduce DA release and elicit hypomotility. The potency of the drugs and their effectiveness is similar in the two areas. Inhibition of DA release appears related to the ability of the various agonists to stimulate D-2 rather than D-1 receptors. Thus, the reportedly selective D-1 agonist, SKF 38393, was inactive on DA release and metabolism even at doses fully active in eliciting D-1-mediated effects (grooming); on the other hand apomorphine, a D-1/D-2 agonist, and pergolide, a D-2 agonist with rather weak D-1 activity, reduced DA release in a manner which was related to their agonist activity at D-2 receptors; finally LY 171555, (+)-3PPP and BHT 920, which selectively stimulate D-2 receptors, were fully active at reducing DA release in vivo. Apomorphine, pergolide, LY 171555 and (+)-3PPP given at higher doses elicited behavioral stimulation. In contrast, BHT 920 failed to do so. In further contrast (-)-3PPP (0.1-10 mg/kg s.c.), which failed to reduce DA release at low doses, actually stimulated it at high doses (10 mg/kg s.c.) and elicited hypomotility, thus resembling DA receptor antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗