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Biomedical subjects

F M Scalzo

Publications and source records attributed to F M Scalzo.

At least 19 recordsLinked to original sources
PubMed2001

Interactions of inflammatory pain and morphine in infant rats: long-term behavioral effects.

Neonatal rat pups exposed to repetitive acute pain show decreases in pain threshold and altered behavior during adulthood. A model using prolonged inflammatory pain in neonatal rats may have greater clinical relevance for investigating the long-term behavioral effects of neonatal pain in ex-preterm neonates. Neonatal rat pups were exposed to repeated formalin injections on postnatal (P) days 1-7 (P1-P7), with or without morphine pretreatment, and were compared with untreated controls. Behavioral testing during adulthood assessed pain thresholds using hot-plate (HP) and tail-flick (TF) tests, alcohol preference, and locomotor activity (baseline and postamphetamine). Adult rats exposed to neonatal inflammatory pain exhibited longer HP latencies than controls and male rats had longer HP thresholds compared to females. Male rats exposed to neonatal morphine alone exhibited longer TF latencies than controls. Both neonatal morphine treatment and neonatal inflammatory pain decreased ethanol preference, but their effects were not additive. During adulthood, male rats exposed to neonatal inflammatory pain exhibited less locomotor activity than untreated controls. We conclude that neonatal formalin and morphine treatment have specific patterns of long-term behavioral effects in adulthood, some of which are attenuated when the two treatments are combined.

Alcohol Drinking↗
PubMed2000

Can adverse neonatal experiences alter brain development and subsequent behavior?

Self-destructive behavior in current society promotes a search for psychobiological factors underlying this epidemic. Perinatal brain plasticity increases the vulnerability to early adverse experiences, thus leading to abnormal development and behavior. Although several epidemiological investigations have correlated perinatal and neonatal complications with abnormal adult behavior, our understanding of the underlying mechanisms remains rudimentary. Models of early experience, such as repetitive pain, sepsis, or maternal separation in rodents and other species have noted multiple alterations in the adult brain, correlated with specific behavioral phenotypes depending on the timing and nature of the insult. The mechanisms mediating such changes in the neonatal brain have remained largely unexplored. We propose that lack of N-methyl-D-aspartate (NMDA) receptor activity from maternal separation and sensory isolation leads to increased apoptosis in multiple areas of the immature brain. On the other hand, exposure to repetitive pain may cause excessive NMDA/excitatory amino acid activation resulting in excitotoxic damage to developing neurons. These changes promote two distinct behavioral phenotypes characterized by increased anxiety, altered pain sensitivity, stress disorders, hyperactivity/attention deficit disorder, leading to impaired social skills and patterns of self-destructive behavior. The clinical important of these mechanisms lies in the prevention of early insults, effective treatment of neonatal pain and stress, and perhaps the discovery of novel therapeutic approaches that limit neuronal excitotoxicity or apoptosis.

Adult↗
PubMed1998

Gestational exposure to cocaine or pharmacologically related compounds: effects on behavior and striatal dopamine receptors.

Gestational cocaine (COC) exposure has been reported to alter behavior and possibly dopamine (DA) receptors. In this paper, we further examined the effects of prenatal COC (40 mg/kg, s.c.) on DA receptor binding and the behavioral response to quinpirole, a DA D2 receptor agonist. In an attempt to elucidate possible mechanisms of such effects, we exposed pregnant dams to specific reuptake blockers; fluoxetine 12.5 mg/kg, a serotonin reuptake blocker; desipramine 10 mg/kg, a norepinephrine reuptake blocker; GBR-12909 10 mg/kg, a DA reuptake blocker; or to a local anesthetic, lidocaine 40 mg/kg. Drugs were administered once daily over gestational days 8-20. Control dams were injected with saline (SAL) or pair-fed to the COC group. Quinpirole challenge was performed in the offspring on post natal day 19. Two pups per litter were injected (s.c.) with 0.03 or 0.09 mg/kg quinpirole-HCl on post-natal day 19. The remaining pups in each litter were sacrificed for analysis of striatal DA receptors. Results showed that only COC exposure altered the behavioral response to the quinpirole challenge by increasing quinpirole-induced stereotypy and motor activity relative to SAL controls. DA receptor analysis showed no alteration in K(D) or B(MAX) for striatal D1 or D2 sites in any group. These results suggest that prenatal COC exposure produces alterations in function of the D2 receptor complex which are not reflected in K(D) or B(MAX) and that these effects are not fully mimicked by exposure to specific monoamine reuptake blockers or a local anesthetic.

Animals↗
PubMed1994

The role of NMDA and sigma systems in the behavioral effects of phencyclidine in preweanling rats.

To determine the role of NMDA receptor blockade and sigma receptors in the behavioral effects of PCP during development, we assessed the behavioral effects of PCP, (+)-MK-801 and 1,3-Di(2-tolyl)guanidine (DTG) in preweanling rats. In the first experiment, rats were injected sc on postnatal day (PND) 19 with 0.5-4.5 mg/kg PCP, and locomotor activity and wall climbing behavior were scored. PCP induced high levels of locomotor activity on PND 19 in a dose dependent manner with the 2.0 mg/kg dose producing the greatest activity. In the second experiment, rats were injected on PND 12 or 19 with 1.0-4.0 mg/kg PCP or 0.1-0.4 mg/kg (+)-MK-801 and tested using the same procedures. Both PCP and (+)-MK-801 induced activity increases on PND 19 in a dose dependent manner, with 2.0 and 3.0 mg/kg PCP and 0.2 mg/kg (+)-MK-801 inducing the highest activity levels. Peak activity levels on PND 12 were approximately 30% of those observed on PND 19, with the lowest dose of PCP and (+)-MK-801 producing the greatest activity. Large amounts of wall climbing behavior were elicited by PCP on PND 12, whereas (+)-MK-801 induced only minor amounts of wall climbing. In the third experiment, the effects of 0, 1, 3, 6, or 12 mg/kg DTG were examined in PND 13-14 and 16-17 rats. DTG had little effect on locomotor activity on PND 13-14, although the highest dose did inhibit activity. On PND 16-17, all doses of DTG tended to increase locomotor activity. The results suggest (1) the robust locomotor effects of PCP on PND 19 are mediated in part by NMDA mechanisms (2) this period of increased sensitivity to both PCP and (+)-MK-801 might represent a critical period of development when systems mediating locomotor activity are vulnerable to neurotoxic insult (3) NMDA blockade alone does not mediate PCP-induced wall climbing behavior and (4) that at the doses of DTG and the ages tested, sigma receptors do not play a role in the locomotor-inducing effects of PCP.

Animals↗
PubMed1993

Effects of labetalol on cocaine pharmacokinetics in neonatal piglets.

Developmental exposure to cocaine can produce adverse neurobehavioral and cardiovascular effects. Few animal models of human neonatal exposure have been established. A pharmacokinetic study was therefore conducted to characterize the disposition of cocaine and a major metabolite benzoylecgonine (BE) using piglets as an animal model. Eight piglets (postnatal days 8-9) were instrumented with a jugular cannula for drug administration and blood sampling. One group of subjects (controls) received 6.0 mg/kg of cocaine-HCl (i.v.) and blood samples were drawn over 0-24 h. In another group (labetalol), 0.25 mg/kg labetalol-HCl was coadministered 15 min following cocaine dosing. Plasma levels of cocaine and BE were determined using GC-MS methods. Pharmacokinetics were evaluated by using a model-independent approach and compartmental modeling. For controls model-independent results were as follows: AUC = 148.9 +/- 9.0 mg/l x min, systemic clearance = 0.041 +/- 0.003 liters/min/kg, volume of distribution = 1.543 +/- 0.470 liters/kg, and t1/2 beta = 29.4 +/- 6.8 min. Cocaine followed two-compartment model kinetics with distribution and elimination half-lives of 0.3 +/- 0.1 and 58.0 +/- 18.0 min, respectively. Labetalol significantly decreased systemic clearance to 0.029 +/- 0.004 liters/min/kg. BE kinetics revealed a elimination half-life of 230.0 +/- 83.2 min. The results demonstrate a rapid distribution and metabolism of cocaine to BE followed by a prolonged elimination phase which is extended by labetalol treatment.

Animals↗
PubMed1993

Haloperidol effects on the developing dopamine system: conflicting results and implications for neurobehavioral teratology research.

In an attempt to further develop basic principles to guide research in neurobehavioral teratology, six experiments were conducted to examine the effects of prenatal haloperidol (a D2 dopamine antagonist) exposure on striatal D1 and D2 binding sites. Another laboratory has repeatedly reported that prenatal exposure to this dopamine antagonist reduces striatal dopamine binding sites in exposed offspring. Our initial studies were successful in replicating and extending these previously reported reductions in D2 dopamine binding sites in caudate of rats exposed prenatally to haloperidol. However, additional experiments in our laboratory, in which pups were exposed to a range of haloperidol doses over gestational periods when the dopamine system has been reported to be most vulnerable to prenatal haloperidol exposure effects, have repeatedly failed to replicate our initial findings. Three other laboratories have also failed to duplicate this effect. The results of these studies suggest that beyond "standard" confounding variables, neurobehavioral teratologists are faced with as yet poorly understood factors that influence replication of findings within and between laboratories. These findings also emphasize the importance of within- and between-laboratory replication of experimental findings.

Animals↗
PubMed1992

The ontogeny of phencyclidine-induced wall climbing and locomotor activity.

Wall climbing behavior is an age-specific behavior that is elicited during postnatal Days 7 through 17 by various stimuli that include heat, odors, shock, and the catecholaminergic agonists apomorphine, amphetamine, and clonidine. In a previous study, a significant amount of wall climbing behavior was observed during ataxia and activity testing following phencyclidine (PCP) administration in Day 19 but not Day 40 rat pups. The present study describes the ontogeny of PCP-induced wall climbing behavior and locomotor activity. Frequency and duration of wall climbing bouts and locomotor activity were recorded on Days 5, 12, 19, 26, 33, or 40 following PCP treatment. On Day 12, all doses of PCP induced significant amounts of wall climbing behavior. A similar pattern of results was observed on Day 5 although these effects were not statistically significant. After Day 12, PCP-induced wall climbing behavior declined precipitously. PCP increased locomotor activity at all ages tested with maximum activities observed on Day 19. These results demonstrate that PCP-elicited wall climbing behavior follows an ontogenetic profile similar to that previously reported for other stimuli and that there are robust ontogenetic differences in the locomotor response to PCP.

Animals↗
PubMed1992

Cardiovascular responses to feeding in newborn piglets.

Cardiovascular responses to feeding have been observed in several species during various periods of development and have been implicated in the development of cardiovascular regulation. In the rat, these responses are characterized by short-lasting, large increases in blood pressure (BP) and moderate increases in heart rate. These responses appear to be sympathetically mediated because pretreatment with ganglionic blockers eliminates the increase in BP associated with milk ingestion. The present study was designed to determine if similar cardiovascular responses occur during feeding in the newborn piglet. Piglets were obtained on postnatal d 2 and fed a milk diet via automatic feeder 6 times a day. On postnatal d 6, the piglets were instrumented with an external carotid artery catheter and an internal jugular vein catheter. On postnatal d 8 and 9, direct arterial BP and heart rate were recorded during feeding. BP responses to milk ingestion were immediate, and they reached a maximum increase of 50% above baseline on both test days and followed a response profile similar to that previously described in the 15-d-old rat. An increase in heart rate was also observed, reaching a maximum of 42% above baseline. The results show that early in life piglets have large cardiovascular responses to milk ingestion similar to those observed in young rats and human infants. These responses appear to model the cardiovascular responses to feeding observed in human infants and might be useful as a noninvasive method for assessing neonatal autonomic reactivity. These responses also have the potential to cause adverse effects in newborns already at risk for cardiovascular and cerebrovascular disease.

Animals↗
PubMed1991

Pharmacological blockade of blood pressure and heart rate increases following milk ingestion in 15-day-old SHR and WKY rat pups.

The effects of hexamethonium, a ganglionic blocker, on blood pressure (BP) and heart rate (HR) responses to milk ingestion were assessed in awake, 15-day-old spontaneously hypertensive rats (SHR) and their normotensive progenitor strain, Wistar-Kyoto rats (WKY) using two methods of milk delivery. SHRs had larger increases in BP compared to WKYs, but WKYs exhibited larger increases in HR following milk ingestion from an anesthetized dam. BP responses to milk ingestion from a tongue cannula were also larger in SHRs. Administration of hexamethonium prior to milk delivery resulted in a drop in BP following milk ingestion in both milk delivery situations for each strain. The results suggest that SHRs exhibit exaggerated sympathetic activation to milk ingestion compared to WKYs, and that in both strains, cardiovascular responses to feeding are modulated by the presence of the dam.

Animals↗
PubMed1990

Ontogeny of the enhanced behavioral response to amphetamine in amphetamine-pretreated rats.

Repeated administration of amphetamine to adult rats results in enhanced behavioral responses to subsequent amphetamine exposure. These experiments were designed to determine the earliest age at which behavioral sensitization to amphetamine could be detected. Rats from both sexes (n = 6-8/group) at ages of 1, 7, 21 or 49 postnatal days (PNDs) were injected with either d-amphetamine sulfate (5 mg/kg) or saline, SC, twice daily for 5 consecutive days. Stereotyped behavior and locomotor activity responses to a challenge dose of d-amphetamine (2.5 mg/kg), or saline, IP, were assessed for a total of 90 min, 15 days after the last dose of pretreatment. Amphetamine-induced stereotyped behavior was significantly enhanced only when amphetamine pretreatment was initiated at PND 49, but not at the earlier ages of PND 1, 7 or 21. There was no apparent sex difference in this effect. Correspondingly, amphetamine-induced locomotor activity was reduced in both sexes of the same age group (PND 49), but not in groups pretreated earlier, when compared to the saline-pretreated rats. These results suggest that amphetamine sensitization may be a late-developing effect, one which occurs sometime after the 3rd week of postnatal life.

Aging↗
PubMed1990

Weanling rats exposed prenatally to cocaine exhibit an increase in striatal D2 dopamine binding associated with an increase in ligand affinity.

Prenatal exposure to cocaine can result in abnormal neurobehavioral development. This study found an increase in D2 dopamine receptor binding, associated with an increase in ligand affinity, in striatum of weanling rats exposed prenatally to cocaine. There were no changes in D2 receptor binding in nucleus accumbens nor D1 receptor binding in either striatum or nucleus accumbens. Alterations in D2 dopamine receptors may be associated with neurobehavioral alterations following prenatal cocaine exposure.

Animals↗
PubMed1989

Neurochemical effects of prenatal haloperidol exposure.

The neurochemical effects of prenatal exposure to dopamine receptor antagonists are as yet poorly characterized. To further examine this problem, pregnant rats were given daily subcutaneous injections of vehicle, 2.5 or 5.0 mg/kg haloperidol over gestational days 6 through 20. Membrane binding of [3H]SCH-23390 (D1-specific) and [3H]spiroperidol (D2-specific in most brain areas) was measured in four regions of the cerebral dopamine system at postnatal day (PND) 30. Dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels were measured in caudate on PND 30 following a d-amphetamine challenge. Prenatal haloperidol exposure reduced [3H]SCH-23390 and [3H]spiroperidol binding in caudate in a dose-dependent manner. [3H]Spiroperidol binding was similarly reduced in nucleus accumbens, but only the low dose (2.5 mg/kg) group showed decreased [3H]SCH-23390 binding in this region. Binding of neither compound was significantly altered in amygdala or frontal cortex. Basal or drug-stimulated levels of caudate DA and DOPAC were unaltered. It is concluded that prenatal haloperidol exposure reduces D1 and D2 binding in some, but not all regions of the forebrain dopamine system.

Amphetamine↗
PubMed1989

Behavioral effects of prenatal haloperidol exposure.

Pregnant albino rats were exposed to vehicle (CON), 2.5 mg/kg (LOW) or 5.0 mg/kg (HIGH) haloperidol (HAL) from the sixth through the twentieth day of gestation. The effect of prenatal HAL exposure on offspring was assessed with the following five behavioral measures: 1) milk-induced behavioral activation on the sixth postnatal day (PND 6), 2) shock-precipitated wall climbing (PNDs 9, 11, 13, 15 and 17), 3) amphetamine-induced stereotypies (PND 30), 4) apomorphine-induced stereotypies (PND 30) and 5) duration of barbiturate anesthesia (PNDs 34 and 62). Measures taken very early in life indicated that prenatal HAL reduced arousal. Inactivity scores were elevated in HAL-exposed pups on PND 6 during milk-induced behavioral activation. Shock-precipitated wall climbing was reduced in the HAL animals on PNDs 9 and 11, but not thereafter. At PND 30, no prenatal treatment effect was detectable on stimulant-induced stereotypies or on duration of barbiturate anesthesia. On PND 62, barbiturate anesthesia duration was significantly reduced in both sexes of HIGH HAL animals. These findings suggest that prenatal HAL effects follow a dynamic, changing course as the exposed rat pup matures. Early reductions in arousal (milk-induced behavior and shock-precipitated wall climbing) wane with age, perhaps to be replaced by an actual increase in arousal as HAL pups approach adulthood.

Anesthesia↗
PubMed1989

Chronic prenatal haloperidol exposure: lack of effect on presynaptic dopamine autoreceptors.

Prenatal haloperidol exposure in rats is known to reduce striatal D2 receptor binding in postnatal day (PND) 30 offspring. The effects of prenatal haloperidol exposure on presynaptic dopamine (DA) autoreceptor function are not well described. Pregnant albino rats were given daily injections of haloperidol (2.5 or 5.0 mg/kg, sc) or vehicle over gestational days 6-20. Presynaptic DA autoreceptor function was assessed using the DOPA decarboxylase inhibitor NSD-1015 and gamma-butyrolactone in the caudate, nucleus accumbens and olfactory tubercles of male offspring sacrificed on PND 97. There appeared to be no impairment of autoreceptor function in any region studied. The data indicate that prenatal haloperidol exposure does not result in permanent alterations in presynaptic DA autoreceptor function.

4-Butyrolactone↗
PubMed1989

Behavioral and neurochemical effects of orally administered MDMA in the rodent and nonhuman primate.

MDMA (methylenedioxymethamphetamine) is a recreational drug of abuse known as "Ecstasy" which markedly decreases regional brain serotonin (5-HT) content and produces 5-HT nerve terminal degeneration in forebrain areas of the rat. In order to determine the acute and chronic behavioral effects of MDMA, adult rats were given MDMA at 0, 5 or 10 mg/kg, po for 4 consecutive days. Alternatively, parachloroamphetamine (PCA) at 5 mg/kg was administered under the same regimen. Within 30 min after the first dose, the MDMA-treated rats exhibited the serotonin motor syndrome consisting of straub tail and splayed hindlimbs comparable to that seen in the PCA-treated rats. This serotonin motor syndrome, with a duration of about 2 hr, was less pronounced after subsequent doses. At 2-4 wk after the last dose, no significant differences between control and treated rats were seen in emergence, hot plate response, auditory startle response or complex maze behavior even though a significant dose-related decrease (50%) in 5-HT concentration was observed in the frontal cortex and hippocampus of these rats 4 wks after the last dose. Adult female monkeys dosed po with 5 or 10 mg/kg of MDMA twice/day for 4 consecutive days demonstrated no spontaneous behavioral changes or weight loss compared to controls, but forebrain 5-HT concentration was reduced by 80% 1 mon after dosing. These data indicate that at doses only 2-3 times the human dose, MDMA produces significant forebrain 5-HT decreases but does not produce detectable residual behavioral alterations as assessed by these behavioral paradigms.

3,4-Methylenedioxyamphetamine↗
PubMed1988

Blood pressure and heart rate responses of SHR and WKY rat pups during feeding.

These studies measured changes in blood pressure and heart rates of 15-day-old SHR and WKY rat pups immediately following milk ingestion using three different methods of milk delivery. In the first experiment milk ejections were induced, using IV oxytocin, from the pups' natural mothers, while in the second experiment ejections were elicited from Marland Farms Wistar foster mothers. In the last experiment cow's milk was delivered using tongue cannulas and no mother was present. In each case we found that the dramatic increases in blood pressure associated with milk ingestion were larger in the SHR pups, while heart rate changes tended to be larger in the WKY. We also found that the dynamics of these cardiovascular responses to feeding were significantly altered by the presence of the mother.

Animals↗
PubMed1985

Effects of 6-hydroxydopamine-induced catecholamine depletion on shock-precipitated wall climbing of infant rat pups.

Sprague-Dawley rat pups were intracisternally injected with 6-hydroxydopamine (6OHDA) or vehicle on postnatal Day 3 and tested for footshock-precipitated wall climbing behavior every 48 hr from postnatal Days 5 through 17. The 6OHDA treatment was observed to lower brain catecholamine levels, particularly in forebrain, and to decrease the incidence of wall climbing. This attenuation in the amount of wall climbing did not appear to be related to any neurotoxin-induced alterations in general motor activity, body weight, or body temperature. It also did not appear that the depression in wall climbing seen in 6OHDA-treated animals was related to an observed neurotoxin-induced increase in shock sensitivity, given that amount of wall climbing was observed to be positively correlated with footshock intensity. These results provide further support that catecholaminergic systems are involved in the elicitation of wall climbing behavior. The 6OHDA treatment did not alter the ontogenetic time course of disappearance of this behavior pattern, suggesting that maturational changes occurring in forebrain catecholaminergic terminals may not be critical for the dissipation of wall climbing following the second postnatal week.

Animals↗