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P V Piazza

Publications and source records attributed to P V Piazza.

86 records · Page 5Linked to original sources
PubMed1991

Corticosterone levels determine individual vulnerability to amphetamine self-administration.

Individual vulnerability to the reinforcing properties of drugs appears to be an essential characteristic predisposing humans to addiction. In animals, a greater behavioral reactivity to a mild stress, such as exposure to a novel environment, is an index of the vulnerability to acquire amphetamine self-administration. Biological responses to stress as well as behavioral reactivity may predict such a vulnerability. In the present study, rats with a longer duration of corticosterone secretion after exposure to novelty showed facilitation of acquisition of amphetamine self-administration. Furthermore, corticosterone administration in nonpredisposed individuals increased the reinforcing value of the drug and facilitated the acquisition of amphetamine self-administration. These results indicate that the stress-related activity of the hypothalamic-pituitary-adrenal axis may play a role in the pathogenesis of psychostimulant addiction.

Amphetamine↗
PubMed1991

Multiple neurochemical action of clozapine: a quantitative autoradiographic study of DA2, opiate and benzodiazepine receptors in the rat brain after long-term treatment.

The atypical neuroleptic clozapine has clinical and behavioral properties that differ not only from the typical compounds, but also from atypical ones. It interacts with the dopaminergic systems, but also produces effects on the serotoninergic, GABA-ergic, cholinergic systems. In spite of the amount of papers devoted to its study, the profile of the neurochemical action of this drug is still confuse. In this paper we investigated the DA2-, opiate- and benzodiazepine-receptor modifications induced by the long term (21 days) treatment with clozapine 20 mg/kg/day in the rat brain. We found a decrease of DA2 receptor density in the target areas of the mesolimbocortical system (ventral n. caudate-putamen, cerebral cortex except for the anterior cingulate at the most anterior level and the n. accumbens) and a decrease of opiate and benzodiazepine receptors in the cerebral cortex and in the olfactory tubercle. Opiate receptors increase in the patches of the striatum. We also compared these effects with those produced by long-term (21 days), low-dosage (0.5 mg/kg day) haloperidol.

Animals↗
PubMed1990

DA2/NT receptor balance in the mesostriatal and mesolimbocortical systems after chronic treatment with typical and atypical neuroleptic drugs.

Typical and atypical neuroleptic drugs show several clinical and behavioral effects, possibly related to the different anatomical sites of the action in the mesolimbocortical or mesostriatal dopaminergic systems. Because of the interaction between dopamine (DA) and neurotensin (NT) in the target areas of these systems, and in order to study if the different action of typical and atypical neuroleptic drugs could be related to a modification of the DA/NT balance, we investigated DA2 and NT receptor modifications--by means of quantitative receptor autoradiography--after chronic treatment with low dosage of haloperidol, chlorpromazine, thioridazine and clozapine. We described a decrease of NT receptor density in the target areas of the mesolimbocortical system produced by all the treatments. This effect does not match with DA2 receptor modifications. On the contrary, the block of DA transmission obtained by high dosage of haloperidol induces an increase of NT receptor density. Our results further demonstrate the regulation of NT transmission by DAergic drugs.

Animals↗
PubMed1990

Stress- and pharmacologically-induced behavioral sensitization increases vulnerability to acquisition of amphetamine self-administration.

Individual vulnerability to drug addiction may be an important factor in the prognosis of this pathological behavior in man. However, experimental investigations have largely neglected the psychobiological substrate of predisposition to addiction. In this study, we show using a self-administration (SA) acquisition paradigm that previous repeated exposure to a stressful experience (tail-pinch) or to amphetamine, increase the locomotor response to this drug (behavioral sensitization) and enhance vulnerability to acquire amphetamine SA. These results show that vulnerability to develop amphetamine SA may be influenced by stressful experiences, and that previous contact with the drug may enhance a predisposition to amphetamine-taking behavior. As tail-pinch and amphetamine sensitization affect both the dopamine (DA) neural system and the propensity to self-administer amphetamine (behavior also modulated by DA activity), stress may influence SA via an action on the DA system.

Amphetamines↗
PubMed1990

Thioridazine chronic administration: a behavioural and autoradiographic study.

In rats the effects of chronic treatment with thioridazine (5 mg/kg orally administered for 22 days) were studied by means of behavioural supersensitivity to apomorphine and by means of dopamine (DA) receptors quantitative autoradiography. Locomotion and stereotypies induced by apomorphine increased after thioridazine chronic administration, whereas grooming behaviour decreased. Autoradiographic data showed an increase in DA receptors density both in the striatum and in the olfactory tubercle, to which the increase in stereotypies and locomotion could be respectively attributed. DA receptors increased also in the medial and dorsal frontal cortex. Moreover a decrease in DA receptors density appeared in the nucleus accumbens septi and in the lateral frontal cortex. Receptors decrease found in these regions might be associated with thioridazine-induced chronic inactivation of A10 DA neurons, to which the antipsychotic effect of the drug is attributed.

Animals↗
PubMed1990

Chronic thioridazine treatment differently affects DA receptors in striatum and in mesolimbo-cortical systems.

Chronic thioridazine administration (5 mg/kg for 22 days) caused both behavioral and dopamine (DA) receptor modifications in rats. After chronic thioridazine administration, a significant increase in both locomotion and stereotypies induced by apomorphine was observed. In particular, only sniffing increased significantly, whereas grooming behavior decreased and the number of rearings did not change. Autoradiographic data were consistent with the behavioral results. Chronic thioridazine caused an up-regulation of DA receptors both in the striatum and in the olfactory tubercle (O.T.). The striatal effect may account for the increase of stereotypies, whereas the effect in the olfactory tubercle may account for the increase in locomotion. An increase in DA receptors was also found in the medial (MCTX) and dorsal cortex (DCTX). However, a decrease in DA receptors appeared in the nucleus accumbens septi (NAS) and in the lateral cortex (LCTX). This decrease, selectively localized in the mesolimbic DA system, may represent the neurobiological substrate of the depolarization block observed in A10 neurons after chronic thioridazine treatment.

Animals↗
PubMed1989

Factors that predict individual vulnerability to amphetamine self-administration.

Clinical observations show that there is considerable individual variability in the response to the addictive properties of drugs. This individual variability needs to be taken into account in animal models of addiction. Like humans, only some rats readily self-administer low doses of psychostimulants. The individual animals at risk can be identified on the basis of their response to environmental or pharmacological challenges. This predisposition to develop self-administration can be induced by repeated treatment with amphetamine. These results may help elucidate the neurobiological basis of addiction liability observed in both rats and humans.

Animals↗
PubMed1989

Circling behavior: ethological analysis and functional considerations.

Head-turning and circling movements evoked by substantia nigra (pars compacta) (SNpc) stimulation have been ethologically analyzed in order to attribute a functional meaning to these lateralization processes. It has been shown that these motor acts, separated by a constant interval, may be considered a fixed action pattern. The duration of the single acts depends on the SNpc stimulation parameters: the increase in the stimulus strength produces an increase in the number of turns but does not induce the disappearance of the orientation movement. The body movement is always preceded by the head-movement. Haloperidol administration induces a dose-related increase of the orientation component of the motor pattern. These data together with others in the literature suggest the participation of the SNpc in the mechanism of shift in the focus of attention from one point to another in the contralateral surrounding environment.

Animals↗
PubMed1989

The influence of dopaminergic A10 neurons on the motor pattern evoked by substantia nigra (pars compacta) stimulation.

The influence of the mesolimbic-mesocortical dopaminergic (DA) system on the motor pattern evoked by substantia nigra pars compacta (SNpc) stimulation was studied. Electrical stimulation of the A10 group of neurons caused an inhibitory effect preferentially directed towards the orientation movement. Sulpiride administration at low dosages (50 mg/kg i.p.) did not modify this movement at the basal condition, but abolished the increase of its duration induced by ventral tegmental area (VTA) co-stimulation. Mesolimbic activation opposes the effects of SNpc stimulation, restraining the animal in its antero-posterior axis by means of orientation movement inhibition. The results suggest a role of the DA mesolimbic-mesocortical system in the maintenance of focused attention.

Animals↗
PubMed1988

Facilitatory effect of ventral tegmental area A10 region on the attack behaviour in the cat: possible dopaminergic role in selective attention.

Lateral hypothalamus (LH) stimulation in cats which do not spontaneously attack rats, produces an attack pattern which may be divided into 3 main stages: the first, defined as exploratory time (ET), begins with an environmental search and culminates in orienting towards the prey; in the second, defined as attack time (AT), the cat stalks the rat; the last is the biting stage in which the cat seizes and kills the prey by biting its head and neck. The effects of ventral tegmental area (VTA) stimulation on the latency of the whole sequence and on the different stages of the attack pattern were studied. VTA activation resulted in a significant decrease of biting latency, due to the reduction of exploratory time. Moreover, a significant period of prey fixation, seldom present during LH stimulation alone, was observed after VTA-LH co-stimulation. Sulpiride injection caused the disappearance of VTA effects on the predatory pattern. The results indicate that VTA activation induces a decrease in behaviour related to exploration of the environment, and an increase in the focusing of attention on the prey, which seems an important component in the regulation of the predatory pattern. Pharmacological evidence indicates that the VTA effect is mediated by the mesolimbic-mesocortical dopaminergic (DA) system.

Animals↗
PubMed1987

Inhibitory effect of the ventral tegmental A10 region on the hypothalamic defence reaction: evidence for a possible dopaminergic mediation.

The influence of A10 region neurons of the ventral tegmental area (VTA) on the defence reaction evoked by stimulation of the ventromedial hypothalamic nucleus (VMH) was studied in the cat. The latency of the hissing in the defence reaction increased when the VTA was stimulated both ipsi- and contralaterally. A sulpiride (50mg/kg i.p.) injection totally abolished the VTA-provoked increase of the hissing latency without affecting the basal response.

Animals↗
PubMedDate not supplied

Hippocampal type I and type II corticosteroid receptors are modulated by central noradrenergic systems.

The effects of corticosteroids on various brain functions, including the negative feedback control of hypothalamo-pituitary-adrenal (HPA) axis activity, are mediated by two types of receptors (type I, or mineralocorticoid, and type II, or glucocorticoid) in the central nervous system. Although receptor numbers are thought to be regulated by circulating levels of corticosterone, there may be a direct neural control of corticosteroid receptors. In the present experiments, we demonstrate that 6-OHDA lesioning of noradrenergic (NA) ascending pathways in the pedunculus cerebellaris superior (PCS) reduces corticosterone secretion in response to novelty and increases the number of hippocampal type I corticosteroid receptors in rats 24 hr after adrenalectomy. The same lesion in adrenalectomized animals in which corticosterone levels were maintained within normal limits by corticosterone replacement implants also led to an increase in the number of type I corticosterone receptors and a decrease in the apparent affinity (Kd) of type II receptors in the hippocampus. These results suggest that the NA system may regulate HPA axis activity via a direct control of the number of type I receptors and the apparent affinity of type II receptors in the hippocampus. The possibility that there is a neural control of corticosteroid receptors may throw light on mechanisms controlling HPA axis activity and may suggest other approaches to the treatment of dysregulation of the HPA axis observed during stress and in certain psychopathological conditions.

Adrenalectomy↗
PubMedDate not supplied

Experimental approach to individual vulnerability to psychostimulant addiction.

Vulnerability to the development of drug-intake has been studied by using the acquisition of intravenous amphetamine self-administration in the rat. In a series of neurobiological experiments we provoked imbalances in the functioning of the dopaminergic (DA) network by performing lesions of the DA cell bodies in the ventral tegmental area, DA terminals in the amygdala or median raphe nucleus. These imbalances which resulted in enhanced DA transmission ratio between the nucleus accumbens and the prefrontal cortex led to an increase in the rapidity of self-administration acquisition. With a psychobiological approach, we showed that individual differences in vulnerability to develop self-administration in rats of the same strain were correlated with locomotor responses to stress and to an acute injection of amphetamine. Moreover, activation of DA transmission by repeated amphetamine injections changed animals resistant to drug-intake into vulnerable ones. It is suggested that some inherited or acquired factors, at least in part by affecting the activity of DA network, can predispose individuals to drug abuse.

Amphetamines↗