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P V Piazza

Publications and source records attributed to P V Piazza.

At least 55 records · Page 3Linked to original sources
PubMed1997

Glucocorticoids and behavioral effects of psychostimulants. II: cocaine intravenous self-administration and reinstatement depend on glucocorticoid levels.

Observations suggest that corticosterone, the principal glucocorticoid hormone in the rat, can modulate the behavioral effects of drugs of abuse. In this report, the influence of corticosterone on intravenous self-administration of cocaine was studied. In the first experiment, cocaine intravenous self-administration in adrenalectomized rats and in adrenalectomized rats receiving corticosterone replacement treatments was studied as a function of corticosterone concentrations and as a function of cocaine doses (0.025, 0.05, 0.1, 0.2, 0.4, 0.8 mg/kg/infusion). In a second experiment, we tested, in intact rats, the effect of different doses of corticosterone (0.09, 0.18, 0.37, 0.58, 0.75 mg/kg) on the reinstatement of an extinguished cocaine self-administration behavior. It is reported that adrenalectomy markedly shifts the cocaine self-administration dose-effect curve downward. This effect was dose-dependently reversed by corticosterone; a complete restoration being obtained for corticosterone levels in the range of those induced by stress. Corticosterone administration also precipitated dose-dependently the reinstatement of cocaine self-administration. The maximal effect was obtained for a dose of corticosterone producing an increase in plasma levels similar to the increase produced by an intense stress. In conclusion, our results show that glucocorticoids facilitate the reinforcing effects of cocaine and support the hypothesis that glucocorticoids are one of the biological factors determining vulnerability to substance abuse.

Animals↗
PubMed1996

Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic dopaminergic transmission.

Specific antagonists of central dopaminergic receptors constitute the major class of antipsychotic drugs (APD). Two principal effects of APD are used as criteria for the pre-clinical screening of their antipsychotic action: (i) inhibition of basal and depolarization-induced activity of mesolimbic dopaminergic neurons; (ii) antagonism of the locomotor effects of dopaminergic agonists. Given that glucocorticoid hormones in animals increase dopamine release and dopamine-mediated behaviors and that high levels of glucocorticoids can induce psychotic symptoms in humans, these experiments examined whether inhibition of endogenous glucocorticoids might have APD-like effects on mesolimbic dopaminergic transmission in rats. It is shown that suppression of glucocorticoid secretion by adrenalectomy profoundly decreased (by greater than 50%): (i) basal dopaminergic release and the release of dopamine induced by a depolarizing stimulus such as morphine (2 mg/kg, s.c.), as measured in the nucleus accumbens of freely moving animals by microdialysis; (ii) the locomotor activity induced by the direct dopaminergic agonist apomorphine. The effects of adrenalectomy were glucocorticoid specific given that they were reversed by the administration of glucocorticoids at doses within the physiological range. Despite its profound diminution of dopaminergic neurotransmission, adrenalectomy neither modified the number of mesencephalic dopaminergic neurons nor induced gliosis in the mesencephalon or in the nucleus accumbens, as shown by tyrosine hydroxylase and glial fibrillary acidic protein immunostaining. In conclusion, these findings suggest that blockade of central effects of glucocorticoids might open new therapeutic strategies of behavioral disturbances.

Adrenalectomy↗
PubMed1996

Glucocorticoids have state-dependent stimulant effects on the mesencephalic dopaminergic transmission.

An increase in the activity of mesencephalic dopaminergic neurons has been implicated in the appearance of pathological behaviors such as psychosis and drug abuse. Several observations suggest that glucocorticoids might contribute to such an increase in dopaminergic activity. The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on locomotor activity, a behavior dependent on accumbens dopamine. Given that glucocorticoids have certain state-dependent neuronal effects, their action on dopamine was studied in situations differing in dopaminergic tonus, including during the light and dark phases of the circadian cycle, during eating, and in groups of animals differing in their locomotor reactivity to novelty. Dopaminergic activity is increased in the dark period, further increased during food-intake, and is higher in rats defined as high responders to novelty than in low responders. Corticosterone, peripherally administered in a dose that approximates stress-induced plasma concentrations, increased extracellular concentrations of dopamine, and this increase was augmented in the dark phase, during eating, and in high responder rats. Corticosterone had little or no effects in the light phase and in low responder rats. Corticosterone also stimulated locomotor activity, an effect that paralleled the release of dopamine and was abolished by neurochemical (6-hydroxydopamine) depletion of accumbens dopamine. In conclusion, glucocorticoids have state-dependent stimulant effects on mesencephalic dopaminergic transmission, and an interaction between these two factors might be involved in the appearance of behavioral disturbances.

Animals↗
PubMed1996

Acute pharmacological blockade of corticosterone secretion reverses food restriction-induced sensitization of the locomotor response to cocaine.

Several data indicate that a blockade of stress-induced corticosterone secretion prevents the development of the stress-induced sensitization of the behavioral effects of drugs of abuse. In this report we investigated if an acute blockade of corticosterone secretion could reverse stress-induced sensitization once it is already established. Food restriction (90% of initial body weight) was used as stressor. Corticosterone secretion was blocked by the corticosterone synthesis inhibitor metyrapone (100 mg/kg). After 8 days of food restriction, animals received an injection of metyrapone and 3 h later they were tested either for the locomotor response to cocaine or for the corticosterone secretion in response to stress (restraint, 30 min). Neither metyrapone nor food restriction had any effect on the locomotor response to a saline injection. In contrast, food-restricted animals, compared to ad libitum-fed controls, showed a higher locomotor response to cocaine and higher corticosterone levels. Treatment with metyrapone totally abolished these effects. Food-restricted animals, receiving a single injection of metyrapone, did not differ from ad libitum-fed controls for both locomotor response to cocaine and corticosterone secretion. Metyrapone treatment also similarly reduced the response to cocaine and corticosterone secretion in ad libitum-fed controls. In conclusion, this study provides further evidence that the enhancement in drug effects produced by stress depends on an increase in corticosterone levels. Since stress-induced sensitization is considered one of the conditions predisposing to drug abuse, the present results might have implications for the treatment of addiction.

Animals↗
PubMed1996

Maternal glucocorticoid secretion mediates long-term effects of prenatal stress.

There is growing evidence that stressors occurring during pregnancy can impair biological and behavioral adaptation to stress in the adult offspring. Mechanisms by which stress in the pregnant rat can influence development of the offspring are still unknown. In the present study, we investigated the involvement of maternal corticosterone secretion during pregnancy on the hypothalamo-pituitary-adrenal axis activity of adult offspring. We investigated stress-induced corticosterone secretion and hippocampal type I and type II corticosteroid receptors in male adult rats submitted to prenatal stress born to either mothers with intact corticosterone secretion or mothers in which stress-induced corticosterone secretion was blocked by adrenalectomy with substitutive corticosterone therapy. Repeated restraint during the last week of pregnancy was used as prenatal stressor. Furthermore, the specific role of an injection of corticosterone before the restraint stress on adrenalectomized mothers with substitutive corticosterone treatment was also studied. We report here that blockade of the mother's stress-induced glucocorticoid secretion suppresses the prolonged stress-induced corticosteroid response and the decrease in type I hippocampal corticosteroid receptors usually observed in prenatally stressed adults. Conversely, corticosterone administered during stress, to mothers in which corticosterone secretion is blocked, reinstates the effects of prenatal stress. These results suggest for the first time that stress-induced increases in maternal glucocorticoids may be a mechanism by which prenatal stress impairs the development of the adult offspring's glucocorticoid response.

Adrenal Cortex Hormones↗
PubMed1996

Dose-dependent aversive and rewarding effects of amphetamine as revealed by a new place conditioning apparatus.

Amphetamine-induced place conditioning was evaluated in mice using a newly designed apparatus. It was demonstrated that this apparatus provides a neutral set of cues devoid of rewarding or aversive properties and can reveal place preference or aversion after pairings with drugs (amphetamine and morphine for preference and naloxone for aversion) known to produce such effects. Moreover, repeated pairings of environmental cues with either 2 or 3 mg/kg d-amphetamine resulted in significant conditioned place preference on a drug free test, whilst repeated pairings with a lower dose of the drug (1 mg/kg) resulted in significant conditioned place aversion. Finally, a small number of mice showed opposite responses in comparison with group means at low as well as at high doses of amphetamine. These results suggest that amphetamine may promote conditioned place preference or avoidance depending on dosage and individual susceptibility.

Amphetamine↗
PubMed1996

Behavioral reactivity to novelty during youth as a predictive factor of stress-induced corticosterone secretion in the elderly--a life-span study in rats.

Inter- and intra-individual differences in hypothalamo-pituitary adrenal (HPA) axis activity and behavioral reactivity to novelty between young and old rats were evidenced in this longitudinal life-span study. Higher responders to novelty (HR) had a higher corticosterone secretion which showed a quicker increase with age than did the others (LR); the differences in response to novelty observed in youth were no longer apparent in the old rats. Response to novelty in youth is a predictive factor of accelerated aging of the HPA axis. These early changes, which precede the appearance of the memory deficits, may be a causal factor. Disappearance of behavioral and endocrinological inter-individual differences at 21 months highlights the importance of not restricting aging studies to old subjects.

Aging↗
PubMed1996

Pathophysiological basis of vulnerability to drug abuse: role of an interaction between stress, glucocorticoids, and dopaminergic neurons.

Research on drug abuse has recently focused on understanding the vulnerability to develop addiction that is present in certain individuals. These investigations suggest that addiction results from an interaction between drugs and specific individual substrates. Differences in the propensity to develop drug intake can be demonstrated in animals with equal access to drugs under stable laboratory conditions and can be predicted by drug-independent behaviors. Stress, corticosterone, and mesencephalic dopaminergic neurons seem to be organized in a pathophysiological chain determining such a vulnerability. An increased corticosterone secretion, or a higher sensitivity to the effects of this hormone, either naturally present in certain individuals or induced by stress in others, increases the vulnerability to develop drug intake, via an enhancement of the activity of mesencephalic dopaminergic neurons. These findings suggest that addiction therapies should counteract the biological peculiarity that leads some individuals to respond in a pathophysiological way to drugs.

Animals↗
PubMed1996

Novelty-seeking in rats--biobehavioral characteristics and possible relationship with the sensation-seeking trait in man.

A behavioral trait in rats which resembles some of the features of high-sensation seekers in man has been characterized. Given that the response to novelty is the basis of the definition of sensation-seeking, individual differences in reactivity to novelty have been studied on behavioral and biological levels. Certain individuals labeled as high responders (HR) as opposed to low responders (LR) have been shown to be highly reactive when exposed to a novel environment. These groups were investigated for free-choice responses to novel environments differing in complexity and aversiveness, and to other kinds of reinforcement, i.e. food and a drug. The HR rats appeared to seek novelty, variety and emotional stimulation. Only HR individuals have been found to be predisposed to drug-taking: they develop amphetamine self-administration whereas LR individuals do not. They also exhibit a higher sensitivity to the reinforcing properties of food. On a biological level, compared to LR rats, HR animals have an enhanced level of dopaminergic activity in the nucleus accumbens both under basal conditions or following a tail-pinch stress. HR and LR rats differ in reactivity of the corticotropic axis: HR rats exposed to a novel environment have a prolonged secretion of corticosterone compared to LR rats. The association of novelty, drug and food seeking in the same individual suggests that these characteristics share common processes. Differences in dopaminergic activity between HR and LR rats are consistent with results implicating these dopaminergic neurons in response to novelty and in drug-taking behavior. Given that rats self-administer corticosterone and that HR rats are more sensitive to the reinforcing properties of corticosteroids, it could be speculated that HR rats seek novelty for the reinforcing action of corticosterone. These characteristics may be analogous to some for the features found in human high-sensation seekers and this animal model may be useful in determinating the biological basis of this human trait.

Animals↗
PubMed1995

Social stress increases the acquisition of cocaine self-administration in male and female rats.

The effect of social stress on the vulnerability to commence cocaine self-administration was examined in Sprague-Dawley rats repeatedly exposed to aggressive attack by a same-sex opponent. Both sexes were studied, since the factors influencing the acquisition of drug self-administration in females have not been defined. Male and female rats encountered an aggressive male or lactating female opponent on four separate occasions over the course of one week. Control male and female rats were not exposed to attack. All animals were implanted with jugular catheters, and six days later placed into the self-administration box, where a nose-poke in the designated 'active hole' resulted in a 20 microliters injection of cocaine (0.32 mg/kg). Nose-pokes in an 'inactive' hole had no effect. Male and female rats that had experienced social stress self-administered more cocaine than non-defeated controls. The difference between the stressed and non-stressed animals in the number of cocaine injections was not present during the first few days of exposure to cocaine, but became more pronounced over time. Social stress increased the number of responses for cocaine, but did not alter the number of non-specific responses. Sex differences in self-administration were not significant. Therefore, social status appears to be a potent influence in the onset of drug taking behavior in both male and female rats.

Aggression↗
PubMed1995

Opposite effects on hippocampal corticosteroid receptors induced by stimulation of beta and alpha 1 noradrenergic receptors.

Central corticosteroid receptors play an important role in the regulation of the secretion of corticosterone. Although these receptors are thought to be regulated by circulating levels of corticosterone, there is evidence for direct neural control. For example, it has been shown that noradrenergic lesions can both increase and decrease corticosteroid receptors depending on the brain structure involved. In the present study, we investigated the role of different noradrenergic receptors in the rat, by examining the effect of the acute administration of agonists and antagonists of beta and alpha 1 noradrenergic receptors on hippocampal type I and type II corticosteroid receptor levels. The effects of these drugs were studied in adrenalectomized animals whose plasma levels of corticosterone were maintained in the physiological range by implantation of coritcosterone pellets. Our results show that the beta receptor agonist salbutamol (5 mg/kg) increased the number of type I and type II hippocampal corticosteroid receptors. This effect was blocked by the beta receptor antagonist propranolol (5 mg/kg), which had no effect on its own. In contrast, the alpha 1 receptor agonist phenylephrine (100 micrograms) reduced the number of type I and type II corticosteroid receptors, whereas the alpha 1 receptor antagonist prazosin (0.5 mg/kg) increased type I receptors. The effect of prazosin was attributed to an increase in the relative beta tonus resulting from blockade of alpha 1 receptors. Its effect was reversed by the simultaneous injection of the beta receptor antagonist propranolol. In conclusion, our results show that noradrenergic transmission can have both a facilitatory and an inhibitory action on central corticosteroid receptors by acting respectively on beta and alpha 1 noradrenergic receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1995

Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion.

Repeated exposures to stress sensitize motor and addictive effects of drugs of abuse. Recently, it has been shown that stress-induced behavioral sensitization depends on the secretion of glucocorticoids. We investigated if sensitization of dopamine-dependent effects of psychostimulants and opioids was influenced by glucocorticoid. Sensitization of the dopaminergic response to drugs is considered the neural substrate of behavioral sensitization and has been implicated in vulnerability to drug abuse. Dopamine-dependent effects of psychostimulants and opioids were evaluated by injecting either amphetamine into the nucleus accumbens (10 micrograms/side) or morphine into the ventral tegmental area (VTA) (1 microgram/side). The locomotor response to psychostimulants and opioids injected in these brain areas depends on the mesencephalic dopaminergic transmission. Drug-induced locomotion was compared in male rats in which corticosterone secretion was either in +tct or experimentally suppressed by an adrenalectomy associated with a substitutive treatment reproducing basal levels of the hormone. Eight days of food restriction (80% of the initial body weight) were used as a stressor. Suppression of stress-induced corticosterone secretion abolished food restriction-induced sensitization of the locomotor effects of intra-accumbens amphetamine and intra-VTA morphine. This effect was corticosterone dependent since the restoration of corticosterone levels in the range of those induced by stress totally reinstates sensitization. Our results suggest that glucocorticoids control stress-induced sensitization by changing the sensitivity of the mesencephalic dopaminergic transmission to drugs of abuse. Since dopaminergic effects of drugs are related to their addictive properties, secretion of glucocorticoids may be one of the factors determining the enhanced vulnerability to drugs observed in stressed subjects.

Amphetamine↗
PubMed1995

Stress-induced sensitization and glucocorticoids. II. Sensitization of the increase in extracellular dopamine induced by cocaine depends on stress-induced corticosterone secretion.

Secretion of glucocorticoids seems to control stress-induced sensitization of the behavioral effects of drugs of abuse by acting on the mesencephalic dopaminergic transmission, the principal neural substrate of sensitization. In order to investigate the mechanisms of this interaction between glucocorticoids and dopamine, we studied the sensitization of the increase in extracellular concentration of dopamine induced by cocaine in male rats in which corticosterone secretion was either intact or blocked. Extracellular concentrations of dopamine were evaluated in the nucleus accumbens of freely moving animals by means of microdialysis. Metyrapone, an inhibitor of corticosterone synthesis, was used to block stress-induced corticosterone secretion. Food-restriction (90% of the initial body weight) was the stressor used to induce sensitization. It was found that metyrapone (100 mg/kg s.c. twice a day for 8 d) suppressed stress-induced sensitization of the increase in accumbens dopamine induced by cocaine (10 mg/kg, i.p.) and sensitization of cocaine-induced locomotion Metyrapone suppressed both the development and the expression of sensitization. Thus, sensitization was equally blocked when the metyrapone treatment started either 1 d before the start of food-restriction or 8 d later, that is, when food-restriction-induced sensitization to cocaine was already established. In conclusion, our results suggest that glucocorticoids modify sensitization of the behavioral effects of cocaine by acting on extracellular concentrations of dopamine. Since addictive properties of psychostimulants seem mediated by the increase in extracellular concentrations of dopamine they induce, these findings may have implications for the development of new therapeutic strategies of addiction.

Animals↗
PubMed1995

Adoption reverses the long-term impairment in glucocorticoid feedback induced by prenatal stress.

The development of the organism is subjected to critical and complex influences during the perinatal period. Prenatal and postnatal stresses can have different long-term behavioral effects, and appropriate postnatal manipulations can counteract the behavioral effects of prenatal stress. In the present study, we investigated the involvement of changes in the activity of the hypothalamo-pituitary-adrenal (HPA) axis in the long-term effects of prenatal and postnatal events and of interactions between them. We investigated stress-induced corticosterone secretion and hippocampal corticosteroid receptors in male adult rats submitted to prenatal and/or postnatal manipulations. Repeated restraint during the last week of pregnancy was used as prenatal stressor, and adoption at birth was used to change the postnatal environment. We found that (1) prenatal stress prolongs stress-induced corticosterone secretion in adult rats, which was attributed to the observed decrease in central corticosteroid receptors; (2) adoption, irrespective of the stress experience of the foster mother, reverses the effects of prenatal stress; and (3) adoption per se increases maternal behavior and decreases the stress-induced corticosterone secretion peak in the adult offspring. In conclusion, certain prenatal and postnatal manipulations appear to have opposite long-term effects on the activity of the HPA axis, and adoption, probably by modifying maternal behavior, can protect against the effects of prenatal stress. Thus, changes in the activity of the HPA axis may be one of the biological substrates of the long-term effects of certain perinatal events.

Animals↗
PubMed1994

Inhibition of corticosterone synthesis by Metyrapone decreases cocaine-induced locomotion and relapse of cocaine self-administration.

Several studies have recently shown that basal and stress-induced secretion of corticosterone may enhance vulnerability to drugs of abuse. In this report, we studied the effects of metyrapone, an inhibitor of the synthesis of corticosterone, on cocaine-induced locomotion and on the relapse of cocaine self-administration. Locomotor response to cocaine was studied because psychomotor effects of drugs have been shown to be related to their reinforcing properties. Self-administration was studied in the relapse phase since blockade of relapse is central to the therapy of addiction. Before these behavioral tests, rats in different experimental groups were injected subcutaneously with either metyrapone (100 mg/kg) or vehicle, twice a day for 8 days. Metyrapone treatment reduced cocaine-induced locomotor activity and relapse of cocaine self-administration, without inducing a nonspecific disruption of motor or food-directed behaviors. Under these experimental conditions, the metyrapone treatment totally blocked stress-induced corticosterone secretion but did not modify basal corticosterone levels. These results confirm the involvement of glucocorticoids in the pathophysiological mechanisms underlying vulnerability to drug abuse, and may have implications for the development of new therapeutic strategies of drug addiction.

Analysis of Variance↗
PubMed1994

Animals predisposed to develop amphetamine self-administration show higher susceptibility to develop contextual conditioning of both amphetamine-induced hyperlocomotion and sensitization.

It has been shown that rats, like humans, display individual differences in the propensity to develop psychostimulant self-administration. Animals showing the highest locomotor reactivity to novelty (HRs: High Responders) are more prone to develop amphetamine self-administration than rats having a low locomotor response to novelty (LRs: Low Responders). The present study was designed to ascertain whether individual differences are also present in the conditioning of drug effects, a process involved in the maintenance of addiction. After pairing the drug effect with a particular set of environmental cues, only HRs showed conditioned hyperlocomotion and environment-specific sensitization to the effect of amphetamine. Unconditioned sensitization was, however, observed in LRs but not in HRs. The environment-specific sensitization disappeared on extinction of the conditioned hyperlocomotion in HRs, indicating that conditioning facilitates the expression of sensitization. In contrast, an inhibitory influence of conditioning on sensitization emerged from the analysis of the same results over all the experimental groups, without taking individual differences into account. In conclusion, our results show that: (i) locomotor reactivity to novelty predicts both vulnerability to develop self-administration and contextual conditioning of drug effects, which suggests that the two phenomena are two related features and that conditioning plays an important role not only in the maintenance of drug intake but also in its development; (ii) conditioned and unconditioned sensitization can be developed separately in different individuals which suggests that they are independent phenomena; (iii) analysis of individual differences is relevant to pharmacological studies, especially with respect to drugs of abuse.

Amphetamine↗
PubMed1994

Social isolation-induced enhancement of the psychomotor effects of morphine depends on corticosterone secretion.

Short-term social isolation has been shown to increase individual reactivity to addictive drugs, although the biological factors involved in this effect are largely unknown. In this study, we investigated the influence of corticosterone secretion on the effects of social isolation on the response to opioids. The effects of social isolation on morphine-induced locomotor activity were compared in: (i) animals with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) animals in which stress-induced corticosterone secretion was blocked by adrenalectomy. The animals in the latter group were implanted with subcutaneous corticosterone pellets (50 mg), which slowly release corticosterone, producing stable plasma levels within the physiological range. Social isolation increased the locomotor response to morphine (2 mg/kg s.c.) in animals with an intact HPA axis, but not in animals in which corticosterone secretion was blocked. These results suggest that corticosterone secretion is required for the expression of the enhanced locomotor response to opioids induced by isolation. Since an enhanced locomotor reactivity to addictive drugs has been found to be frequently associated with an enhanced vulnerability to drug self-administration, these findings suggest a role for glucocorticoids in the vulnerability to the reinforcing effects of opioids.

Adrenalectomy↗