Biomedical subjects

P V Piazza

Publications and source records attributed to P V Piazza.

At least 73 records · Page 4Linked to original sources

PubMed1994

The D1 dopamine agonist SKF 38393, but not the D2 agonist LY 171555, decreases the affinity of type II corticosteroid receptors in rat hippocampus and ventral striatum.

Type I and type II brain corticosteroid receptors are regulated by adrenal hormones as well as being under neural control. Recent studies have indicated that neurotransmitters such as serotonin and noradrenaline are also involved in the regulation of corticosteroid receptors. In a previous study, we showed that dopamine also modulates activity of the corticosteroid receptor system. In the present study, we examined the roles of the dopamine D1 and D2 receptor subtypes in the regulation of corticosteroid receptors. Adrenalectomized rats whose corticosterone levels were maintained within normal limits by corticosterone replacement implants, were injected intraperitoneally with the D1 agonist SKF 38393 or the D2 agonist LY 171555. Corticosteroid receptors were assayed in the ventral striatum and hippocampus. We have shown that the D1 agonist SKF 38393 decreased type II receptor affinity in both regions, whereas the D2 agonist LY 171555 had no effects. The results show that the influence of the dopaminergic system on corticosteroid receptors appears to be mediated by D1 receptors.

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

PubMed1994

Corticosterone circadian secretion differentially facilitates dopamine-mediated psychomotor effect of cocaine and morphine.

Studies of intravenous self-administration and psychomotor effects of drugs have recently suggested that stress-induced corticosterone secretion may be an important factor determining vulnerability to drugs of abuse. In this report, we studied if basal physiological corticosterone secretion modulates sensitivity to cocaine and morphine, and if changes in the reactivity of mesolimbic dopaminergic (DA) neurons, one of the principal substrates of drug-reinforcing effects, are involved. For this purpose we determined the psychomotor effects of these drugs in animals in which corticosterone secretion was suppressed by adrenalectomy and in adrenalectomized animals submitted to different corticosterone replacement therapies designed to mimic (1) only the diurnal levels of the hormone, obtained by the subcutaneous implantation of 50 mg corticosterone pellets; (2) only the nocturnal levels, obtained by adding corticosterone (50 micrograms/ml) to the drinking solution during the dark period; and (3) the entire circadian fluctuation, obtained by combining the two previous treatments. Locomotor response to cocaine and morphine was studied after both systemic and central injections, into the nucleus accumbens for cocaine and into the ventral tegmental area for morphine. These sites were chosen because stimulant effects of cocaine and morphine injected in these structures are dopamine dependent. Our results show that suppression of corticosterone by adrenalectomy reduced the locomotor response to cocaine and morphine, injected both systemically and centrally. The reinstatement of diurnal levels of corticosterone totally reversed adrenalectomy's effects on the behavioral response to cocaine, whereas the reestablishment of the entire corticosterone circadian fluctuation (diurnal plus nocturnal levels) was necessary to reverse the response to morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1993

Corticosterone in the range of stress-induced levels possesses reinforcing properties: implications for sensation-seeking behaviors.

In both humans and animals certain individuals seek stimuli or situations that are considered stressful and consequently avoided by others. A common feature of such situations is an activation of the hypothalamo-pituitary-adrenal axis leading to secretion of glucocorticoids. Since glucocorticoids have euphoric effects in some individuals and have been shown to potentiate the reinforcing properties of drugs of abuse in animals, we hypothesized that corticosterone secretion during stress-like situations may have reinforcing effects and that a higher sensitivity to the reinforcing effects of glucocorticoids might be a biological basis of sensation seeking. In this report we show that (i) corticosterone has reinforcing properties, as evidenced by the development of intravenous self-administration, (ii) self-administration of corticosterone is observed at plasma levels that are comparable to those induced by stress, and (iii) there are individual differences in corticosterone self-administration, which are related to individual reactivity to novelty and sensitivity to drugs of abuse, behavioral features akin to certain traits of high-sensation seekers. These findings provide insight into the physiological role of glucocorticoids and the biology of sensation seeking and may have clinical implications.

Analysis of Variance↗

PubMed1993

Progeny of mothers drinking corticosterone during lactation has lower stress-induced corticosterone secretion and better cognitive performance.

In order to test the hypothesis that maternal corticosterone influences hypothalamus-pituitary-adrenal (HPA) system activity in the adult rat and behaviors related to it, we induced a moderate increase in maternal plasma level of corticosterone by adding the hormone to the drinking water of the dams (200 micrograms/ml) from the day after delivery to weaning. Our previous experiments have shown that this procedure produces plasma levels of the hormone in the range of those following a mild psychic stress (from 4.3 +/- 0.5 to 9.5 +/- 1.8 micrograms/100 ml in the dams, and from 0.7 +/- 0.1 to 1.2 +/- 0.2 micrograms/100 ml in the pups at 10 days of lactation). Adrenal weights were slightly and temporarily decreased by treatment in both mothers and offspring. Only the male progeny was investigated in this study. Corticosterone-nursed rats had significantly less corticosterone and ACTH in basal conditions and after a 2 min restraint stress at 3 months of age, and showed better performances at weaning and at 1, 2 and 3 months of life in the Morris water maze. Our results demonstrate that a moderate increase in maternal corticosterone during lactation influences the activity of HPA axis and improves spatial learning ability of the adult offspring.

Adrenal Glands↗

PubMed1993

Individual differences in the psychomotor effects of morphine are predicted by reactivity to novelty and influenced by corticosterone secretion.

Clinical observations show that individual vulnerability to the reinforcing properties of drugs plays an important part in the subsequent development of addition. In animals, individual vulnerability to psychostimulants has been found to be predicted by their locomotor response to novelty as well as their corticosterone response. Rats with a high locomotor response to novelty (High Responders or HR) relative to Low Responders (LR), show a higher sensitivity to both the psychomotor and reinforcing effects of psychostimulants and a longer lasting corticosterone secretion in response to stress. In this study, we addressed two main questions. First, does the locomotor response to novelty also predict the psychomotor effects of morphine? Second, do differences in corticosterone secretion underlie individual differences in the stimulant effects of morphine? We compared the locomotor response to morphine (2 mg/kg s.c.) in: (i) HR and LR rats with an intact hypothalamo-pituitary-adrenal (HPA) axis; (ii) HR and LR rats in which stress-induced corticosterone secretion was suppressed by adrenalectomy but basal levels of corticosterone were maintained by implantation of subcutaneous corticosterone pellets. In animals with an intact HPA axis, HR rats showed a higher locomotor response than did LRs to morphine. In animals in which corticosterone secretion was suppressed, the enhanced locomotor response of the HRs to morphine fell to that observed in the LRs. In conclusion our data show that, (1) individual reactivity to novelty can predict individual vulnerability to the psychomotor effects of opioids, and (2) stress-induced corticosterone secretion may play a role in determining individual differences in sensitivity to these drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1993

Basal and stress-induced corticosterone secretion is decreased by lesion of mesencephalic dopaminergic neurons.

There is evidence that certain psychopathological conditions are accompanied by a dysfunction in both the hypothalamo-pituitary-adrenal axis and dopaminergic systems, although the relationship between these two systems is as yet unclear. In the present study we investigated the effect of a specific lesion of dopamine mesencephalic neurons (Ventral Tegmental Area) on basal and stress-induced corticosterone secretion. Three weeks after injection of 6-OHDA, there was a depletion in dopamine in the frontal cortex and in the ventral and dorsal striatum, whereas norepinephrine and serotonin levels were unchanged. The dopamine-lesioned rats exhibited a lower basal and stress-induced corticosterone secretion than the sham-lesioned animals. The results indicate that the dopaminergic system may have a stimulatory influence on the hypothalamo-pituitary-adrenal axis.

Animals↗

PubMed1993

Rats orally self-administer corticosterone.

Corticosterone, the major glucocorticoid in the rat, may modulate the reinforcing properties of addictive drugs as well as act as a positive reinforcer for intravenous self-administration. Since glucocorticoids are generally administered to humans via the oral route, we examined the ability of corticosterone to induce oral self-administration in the rat. In a first experiment, animals with free access to food could choose between a corticosterone solution and water. Three doses (25, 50 and 100 micrograms/ml) were tested. The group receiving the 100 micrograms/ml dose was also submitted to an extinction followed by a reversal test. In a second experiment, we examined whether the reinforcing properties of corticosterone could induce drinking independently of food intake. In the pre-test phase rats had access to food only during a fixed period of the day (11.00 h to 14.00 h). Corticosterone solution (200 micrograms/ml) or tap water were available during this period, with free access to tap water for the rest of the day. During the test period, access to food was shifted forward in time, while the availability of the corticosterone solution remained the same. The first experiment showed that rats preferred a corticosterone solution to tap water, developing self-administration in a dose-dependent manner. This preference could be extinguished, but was regained during the reversal phase. In the second experiment, animals that had access to the corticosterone solution drank more than rats that had access to water in the absence of food. These results indicate that corticosterone has reinforcing properties after oral administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1993

Relationship between schedule-induced polydipsia and amphetamine intravenous self-administration. Individual differences and role of experience.

It has been suggested that drug abuse belongs to a larger class of addictive behaviors, including smoking, eating or gambling, which are mediated by common processes. Since laboratory animals can be induced to develop drug self-administration as well as indulge in compulsive eating or drinking, the present experiments were designed to find out if the same animals were susceptible to both behaviors. Only certain rats develop amphetamine intravenous self-administration (SA), and this susceptibility can be predicted from their enhanced locomotor response in a novel environment. Furthermore, excessive, non-regulatory drinking, referred to as schedule-induced polydipsia (SIP), in response to the periodic delivery of small amounts of food is only observed in certain rats. Since the propensity to SA has been shown to be influenced by experimental factors and testing for SIP was found to modify behavioral and biological parameters related to the propensity for drug-seeking, we also investigated whether experience of SIP influenced the subsequent development of SA. In Expt. 1, the rats that developed SA also acquired SIP, and had a higher locomotor response to novelty. The results of Expt. 2 showed that testing for SIP influenced the predisposition to develop amphetamine SA. When animals were tested for SIP first, the polydipsic rats subsequently failed to acquire SA, and had a reduced locomotor response to novelty. These changes seemed to be specific to the experience of SIP, as individual differences in the locomotor response to novelty were unchanged when animals were housed in standard laboratory conditions over a period of one month between the two tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Psychological↗

PubMed1993

Sensitization to the psychomotor effects of amphetamine and morphine induced by food restriction depends on corticosterone secretion.

Food restriction has been shown to enhance the behavioral sensitivity to addictive drugs. The biological factors involved in this effect are largely unknown. Since food restriction, among other factors, increases corticosterone secretion, the role of this hormone in the effects of food restriction on the response to psychostimulants and opioids was investigated. The effects of food restriction on amphetamine- and morphine-induced locomotor activity were compared in: (i) animals with an intact hypothalamo-pituitary-adrenal axis; (ii) animals in which food restriction-induced corticosterone secretion was suppressed by adrenalectomy, but which received exogenous corticosterone from a subcutaneous implant, which slowly releases corticosterone, producing a stable plasma level within the normal physiological range over a period of 20 days. It was found that food restriction enhanced sensitivity to the psychomotor effects of amphetamine (1 mg/kg i.p.) and morphine (1 mg/kg i.p.) in animals with an intact hypothalamo-pituitary-adrenal axis, but not in animals in which endogenous corticosterone secretion was eliminated. These results suggest that corticosterone secretion may be one of the mechanisms by which food restriction amplifies the behavioral responses to amphetamine and morphine. 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 point to a role for glucocorticoids in the susceptibility to drug abuse.

Adrenalectomy↗

PubMed1993

Higher and longer stress-induced increase in dopamine concentrations in the nucleus accumbens of animals predisposed to amphetamine self-administration. A microdialysis study.

Individual vulnerability to the reinforcing effects of drugs appears to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with high locomotor responses to novelty (high responders, HR) acquire amphetamine SA, while animals with low responses (low responders, LR) do not. In this study we examined by microdialysis whether stress-induced extracellular dopamine (DA) concentrations in the nucleus accumbens differed between these two groups of animals. This neurotransmitter was studied because it is thought to be involved in the reinforcing effects of psychostimulants. Furthermore, previous studies have shown that HR animals have a higher basal DOPAC/DA ratio in the nucleus accumbens and higher extracellular concentrations of dopamine in this structure in response to cocaine. The stress procedure used in this experiment consisted of a 10 min tail-pinch. HR animals displayed a higher and longer stress-induced changes in DA concentrations than the LR group. Regression analysis showed that stress-induced changes in DA levels accounted for 75% of the variance observed in the locomotor response to a novel environment. Since higher DA activity in the nucleus accumbens has been reported in animals in which the propensity to psychostimulant SA is induced by brain lesions or life events, this biochemical modification may be one neurobiological substrate of the predisposition to acquire psychostimulant self-administration.

Amphetamine↗

PubMed1993

The mesolimbic dopaminergic system exerts an inhibitory influence on brain corticosteroid receptor affinities.

Central type I and type II corticosteroid receptors play a principle role in the regulation of corticosterone secretion. Although the binding capacity of these receptors is thought to be regulated essentially hormonally, there is also evidence for a direct neural control. For example, experimental manipulation of central serotoninergic and noradrenergic activities modifies the binding capacity of type I and type II corticosteroid receptors via a corticosterone-independent mechanism. In this study, we tested the effect of lesions of dopaminergic neurons in the ventral tegmental area on corticosteroid receptor binding capacity. The study was performed in adrenalectomized rats whose corticosterone levels were maintained within normal limits by corticosterone pellets and corticosterone in their drinking water during the dark period to generate the circadian rhythm. Binding properties of corticosteroid receptors were analysed in target regions of the lesioned neurons, including the ventral and dorsal striatum. Corticosteroid receptors in the hippocampus were also studied as a control as these lesions do not significantly affect dopamine content in this structure. Three weeks after the lesion, type II corticosteroid receptor affinity was increased in the ventral striatum. There was no effect on receptors in the dorsal striatum or hippocampus. Our results, together with other reports showing that dopamine inhibits the expression of corticosteroid receptors in the anterior pituitary, suggest that dopamine transmission exerts a negative control on central corticosteroid receptors.

Adrenalectomy↗

PubMed1992

Stress-induced sensitization to amphetamine and morphine psychomotor effects depend on stress-induced corticosterone secretion.

Repeated exposure to stressful situations has been shown to increase individual reactivity to addictive drugs. However, the biological factors involved in such stress-induced changes are largely unknown. In this study, we investigated the role of corticosterone in the effects of restraint stress on the response to psychostimulants and opioids. The effects of repeated stress on amphetamine- and 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, but who received exogenous corticosterone from a subcutaneous implant. The implanted pellets (50 mg) slowly release corticosterone producing a stable plasma level within the normal physiological range over a period of 20 days. Restraint stress increased the locomotor response to both amphetamine (1.5 mg/kg i.p.) and morphine (2 mg/kg s.c.) in animals with an intact HPA axis, but not in animals in which stress-induced corticosterone secretion was suppressed. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress amplifies behavioral responses to amphetamine and morphine. 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 point to a role for glucocorticoids in the susceptibility to drug abuse.

Adrenal Glands↗

PubMed1992

Noradrenergic regulation of type-I and type-II corticosteroid receptors in amygdala and hypothalamus.

The effects of glucocorticoids on various brain functions including the negative feedback control of HPA axis are mediated by two types of receptor (type I or mineralocorticoid and type II or glucocorticoid) in the central nervous system. Furthermore, noradrenergic systems have been showed to stimulate the activity of hypothalamo-pituitary-adrenal (HPA) axis. The neural and receptor controls of HPA axis activity are generally thought to be independent. Although receptor numbers, especially type-II receptors, are thought to be regulated by circulating levels of corticosterone, they may also be under direct neural control. Thus, it may be suggested that these two types of control are functionally related and that noradrenergic systems may affect HPA axis activity either directly or indirectly via change in receptor characteristics. A major problem in the interpretation of studies examining neurotransmitter regulation of corticosteroid receptors is that the effects of drugs or brain lesions on receptors levels may be secondary to their effects on adrenocortical function. In order to demonstrate a neuronal control on corticosteroid receptors, we tested the effect of 6-hydroxydopamine lesion of noradrenergic systems in the pedunculus cerebellaris superior in adrenalectomized animals whose corticosterone levels were maintained within normal limits by corticosterone replacement implants. Both types of receptor were assayed in hypothalamus and amygdala. We show that: (1) corticosteroid receptors are influenced by noradrenergic systems; (2) this effect depends on the brain region and the receptor type. After the noradrenergic lesion type-I receptors were reduced in hypothalamus and amygdala, whereas type-II receptor were only increased in hypothalamus while receptor affinities were unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenalectomy↗

PubMed1992

Increased locomotor response to novelty and propensity to intravenous amphetamine self-administration in adult offspring of stressed mothers.

It is suggested that drug addiction is more likely to develop in individuals who are particularly sensitive to the reinforcing effects of drugs. Animal studies of intravenous drug self-administration (SA) have shown that rats display a large range of individual differences in the propensity to develop drug-seeking. Predisposed animals are characterized by a higher locomotor reactivity to both novelty and psychostimulants. In this report, we show that prenatal stress (restraint of the mother during the last week of pregnancy) may contribute to an individual's vulnerability to develop amphetamine self-administration. The adult offspring of stressed mothers exhibited: (i) a higher locomotor response to novelty and to an injection of amphetamine (0.3 mg/kg, i.v.); (ii) a higher level of amphetamine self-administration. The data indicate that individual predisposition to drug-seeking in the adult may be induced by prenatal events.

Amphetamine↗

PubMed1992

Repeated corticosterone administration sensitizes the locomotor response to amphetamine.

Repeated exposures to stressful situations has been shown to increase individual reactivity to psychostimulants, although the biological factors involved in such stress-induced changes are still poorly understood. In this study, we investigated the role of corticosterone in the effects of stress on the response to psychostimulants. We found that repeated corticosterone administration (both 1.5 mg/kg, intraperitoneally and 50 micrograms/ml in drinking water, once per day for 15 days) increased the locomotor response to amphetamine (1.15 mg/kg, i.p.). At the doses used in these experiments, corticosterone administration induced similar increases in plasma levels of the hormone to those induced by stress. These results suggest that corticosterone secretion may be one of the mechanisms by which repeated stress increases the behavioral responses to amphetamine. Since an enhanced reactivity to psychostimulants has been found to be an index of a propensity for drug self-administration and a model of certain psychopathological conditions, these findings point to a role for glucocorticoids in such abnormal states.

Amphetamine↗

PubMed1991

Dopaminergic activity is reduced in the prefrontal cortex and increased in the nucleus accumbens of rats predisposed to develop amphetamine self-administration.

Individual vulnerability to the reinforcing effects of drugs appear to be a crucial factor in the development of addiction in humans. In the rat, individuals at risk for psychostimulant self-administration (SA) may be identified from their locomotor reactivity to a stress situation such as exposure to a novel environment. Animals with higher locomotor responses to novelty (High Responders, HR) tend to acquire amphetamine SA, while animals with the lower responses (Low Responders, LR) do not. In this study, we examined whether activity of dopaminergic (DA) and serotoninergic (5-HT) systems differed between HR and LR animals. These transmitter systems are thought to be involved in the reinforcing effects of psychostimulants. Animals from both groups were sacrificed under basal conditions and after exposure for 30 or 120 min to a novel environment, and the DA, 3,4-dihydroxyphenylacetic acid (DOPAC), 5-HT, and 5-hydroxyindolacetic acid (5-HIAA) contents were determined in the prefrontal cortex, nucleus accumbens and striatum. The HR rats displayed a specific neurochemical pattern: a higher DOPAC/DA ratio in the nucleus accumbens and striatum and a lower one in the prefrontal cortex. Furthermore, HR animals had lower overall 5-HT and 5-HIAA levels, corresponding to the mean of these compounds for the three structures studied over the three environmental conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

PubMed1991

Hippocampal type I and type II corticosteroid receptor affinities are reduced in rats predisposed to develop amphetamine self-administration.

It has been suggested that individual predisposition to develop amphetamine self-administration is associated with impairment in corticosteroid negative feedback mechanisms. Since corticosteroid receptors, particularly those in the hippocampus, are involved in corticosterone feedback sensitivity, we examined the relation between individual differences in amphetamine self-administration and characteristics of hippocampal corticosteroid receptors. Rats were selected on the basis of likelihood to self-administer amphetamine and designed as: (1) High Responding (HR) rats, who quickly acquire the response and (2) Low Responding (LR), who fail to self-administer amphetamine. We found lower affinities both for hippocampal type I and type II corticosteroid receptors in the HR animals. These data suggest that modification of hippocampal corticosteroid receptors may be responsible for the predisposition of some animals for amphetamine self-administration. Because HR rats also show a greater behavioral and endocrinological response in a novel environment, these differences in affinities suggest a relation among amphetamine self-administration, control of the corticosterone feedback loop, serum levels of corticosterone and characteristics of hippocampal corticosteroid receptors. The implication is that pharmacological manipulations of corticosteroid receptors may reveal new therapeutic strategies for drug abuse.

Adrenalectomy↗

PubMed1991

Life events-induced decrease of corticosteroid type I receptors is associated with reduced corticosterone feedback and enhanced vulnerability to amphetamine self-administration.

In this study, we attempted to find out whether a social stress-induced increase in the vulnerability to acquire amphetamine self-administration was associated with a change in number of hippocampal corticosteroid receptors. This was examined in two types of sex-mixed colonies of rats. Animals were maintained for 4 weeks in: (1) 'stable social condition', membership did not change after constitution of the colony; (2) 'unstable social condition', the males were changed daily in a random design. The animals living in the 'stable social' conditions had: (1) a lower number of hippocampal type I corticosteroid receptors; (2) a longer duration of the increase in plasma corticosterone after exposure to novelty; (3) a higher vulnerability to acquire amphetamine self-administration. These findings suggest that a decrease in hippocampal type I corticosteroid receptors may be one of the biological mechanisms responsible for the impaired corticosterone feedback control observed in vulnerable animals. These findings throw more light on the role of hypothalamo-pituitary-adrenal axis in the modulation of adaptive behavior. The availability of drugs which are specific for corticosteroid receptors could represent a new approach to the therapy of certain behavioral disturbances.

Adrenalectomy↗