PubMed Health⌕ Search

Biomedical subjects

S B Sparber

Publications and source records attributed to S B Sparber.

At least 19 recordsLinked to original sources
PubMed1999

OCD-Like behaviors caused by a neuropotentiating transgene targeted to cortical and limbic D1+ neurons.

To study the behavioral role of neurons containing the D1 dopamine receptor (D1+), we have used a genetic neurostimulatory approach. We generated transgenic mice that express an intracellular form of cholera toxin (CT), a neuropotentiating enzyme that chronically activates stimulatory G-protein (Gs) signal transduction and cAMP synthesis, under the control of the D1 promoter. Because the D1 promoter, like other CNS-expressed promoters, confers transgene expression that is regionally restricted to different D1+ CNS subsets in different transgenic lines, we observed distinct but related psychomotor disorders in different D1CT-expressing founders. In a D1CT line in which transgene expression was restricted to the following D1+ CNS regions-the piriform cortex layer II, layers II-III of somatosensory cortical areas, and the intercalated nucleus of the amygdala-D1CT mice showed normal CNS and D1+ neural architecture but increased cAMP content in whole extracts of the piriform and somatosensory cortex. These mice also exhibited a constellation of compulsive behavioral abnormalities that strongly resembled human cortical-limbic-induced compulsive disorders such as obsessive-compulsive disorder (OCD). These compulsive behaviors included episodes of perseverance or repetition of any and all normal behaviors, repetitive nonaggressive biting of siblings during grooming, and repetitive leaping. These results suggest that chronic potentiation of cortical and limbic D1+ neurons thought to induce glutamatergic output to the striatum causes behaviors reminiscent of those in human cortical-limbic-induced compulsive disorders.

Aggression↗
PubMed1999

Late embryonic ritanserin exposure fails to alter normal responses to immune system stimulation in young chicks.

Prior studies in our laboratory have demonstrated that prenatal treatment with the serotonin2 (5-HT2) antagonist ritanserin is effective in blocking some of the lethal, dysmorphic, cardiovascular, and behavioral consequences of excessive direct or indirect stimulation of 5-HT2 receptors in the developing chicken. The efficacious dose range for ritanserin in these studies had very little or no effect on the above measures of toxicity when administered alone. In the present study, we extend our characterization of ritanserin's potential toxicity, or lack thereof, to include the normal behavioral and endocrine responses to immune system stimulation by the endotoxin lipopolysaccharide (LPS). LPS administration induces a syndrome collectively known as sickness behavior, manifest as altered thermoregulatory processes leading to fever, and increased serum concentrations of neuroendocrine hormones, including corticosterone. These survival-promoting responses to LPS were assessed in young chickens that had been treated with doses of ritanserin ranging from 0 to 2.7 mg/kg on embryonic day 17 (E17). When sickness behavior was assessed in 5-7-day-old chicks 1 h post-LPS injection, E17 ritanserin-treated subjects did not differ from controls. At 4-6 h post-LPS, 4-day-old chicks displayed a robust fever, and E17 ritanserin did not affect the magnitude of this response. Similarly, E17 ritanserin treatment failed to affect corticosterone concentrations 2 h post-LPS in 14-day-old chicks. Thus, ritanserin treatment during late embryogenesis, a time when it is effective against direct and indirect acting 5-HT2 agonists, failed to modify the survival promoting and beneficial interactions between the nervous, endocrine, and immune systems that are elicited following immunostimulation.

Adjuvants, Immunologic↗
PubMed1999

Voltage associated with spontaneous embryonic motility in the developing chicken: an automated characterization during mid-late embryogenesis.

Movement of developing chicken embryos and their associated membranes generates voltage detectable with electrodes inserted just beneath the eggshell. Use of such voltages as a motility indicator offers an embryonic behavioral assessment method less subjective and invasive than observational methods using windows that disrupt substantial portions of the eggshell. We used a computerized signal recording and processing procedure to compare voltages from embryonic Day 12 (E12), E15, and E18 chicken eggs with embryos, assessed on the same day. Larger voltages were recorded from E18 subjects than from E12 or E15 subjects. Because this could have been due to embryonic size (mass) and/or proximity to the electrodes, making age comparisons uninterpretable, we used standard deviation-normalized and Z-score-based data transformations, comparing groups for relative deviations from basal voltages. E18 subjects still appeared more active than E12 subjects, with E15 a transitional age, in contrast to results from earlier window-based studies. The automated assessment method we used could enhance behavioral teratology studies of avian species.

Age Factors↗
PubMed1998

Evidence for a serotonin-mediated effect of cocaine causing vasoconstriction and herniated umbilici in chicken embryos.

Some of cocaine (COC)'s pathophysiological effects on exposed embryos likely result from its vasoconstrictive action, and serotonin2 (5-HT2) agonists such as dimethoxyiodophenylaminopropane (DOI) can mimic these effects. Infusions of COC (5 mg/kg/min) or DOI (0.5 mg/kg/min) for 15 min into chicken eggs with embryos on E15 caused a significant reduction in blood vessel diameters (14 and 30%, respectively). Pretreatment with the 5-HT2 antagonist ritanserin (RIT, 0.9 mg/kg) 18-22 h earlier blocked the effect of COC and blocked or attenuated the effect of DOI. In separate groups of chicken embryos exposed to multiple injections of low doses of COC on E18, herniated umbilici were prominent in hatchlings. A single bolus injection of the same absolute amount of COC did not cause herniated umbilici. An additional experiment replicated the induction of herniated umbilici by multiple injections of COC and demonstrated the probable involvement of 5-HT2 receptors because RIT blocked COC's ability to induce this anomaly. These data suggest that COC's vasoconstrictive effect, via 5-HT2 receptors, may play a mechanistic role in some adverse outcomes in embryos exposed to COC.

Amphetamines↗
PubMed1998

Relationships between midembryonic 5-HT2 agonist and/or antagonist exposure and detour learning by chickens.

The importance of serotonin (5-HT) as both a transmitter and a regulatory signal during development of many species is well established. The availability of 5-HT receptor subtype agonists and antagonists will enable pharmacological dissection of the importance of one or more of the 5-HT receptors for their involvement in the mediation of developmental insults by drugs that are less selective but include actions upon serotonergic function. Such insults include exposure to cocaine or opiate withdrawal, both of which are blocked or attenuated by 5-HT2 antagonists. The 5-HT2 receptor agonist dimethoxyiodophenylaminopropane (DOI), like cocaine, causes vasoconstriction during embryogenesis, herniated umbilici in hatchlings, and altered detour learning by young chickens after injection into eggs at late stages of embryogenesis. The 5-HT2 antagonist ritanserin (RIT) blocks or significantly attenuates these effects. This study describes an effect of DOI on posthatch detour learning when injected earlier during embryogenesis (i.e., on embryonic day 12, E12) which is opposite its effect when injected later (i.e., on E15). Both effects are blocked by an inactive dose of RIT (0.3 mg/kg egg) and by a higher dose of RIT (0.9 mg/kg egg), which itself retards posthatch detour learning following E12 injection. Thus, excessive stimulation or blockade of 5-HT2 receptors around midembryogenesis can cause a similar behavioral teratogenic outcome. The data are discussed in relation to the likelihood that potential use of 5-HT2 antagonists for treating pregnant women and their fetuses who are not at risk is nil.

Amphetamines↗
PubMed1998

Behavioral and neuroendocrine assessment of ritanserin exposure in the developing chicken: lack of toxicity at effective doses.

The 5-HT2 antagonist ritanserin (RIT) is undergoing Phase III clinical trials for the treatment of substance abuse disorders. RIT has also shown preclinical therapeutic potential for attenuating or blocking lethal and/or toxic effects of exposure to cocaine or the selective 5-HT2 agonist dimethoxyiodophenyl-aminopropane (DOI) in the developing chicken. To assess the potential toxicity ("side effects") of RIT itself during development, we exposed chicken embryos to 0, 0.1, 0.3, 0.9, or 2.7 mg RIT/kg egg by injecting the drug into eggs with 14-day-old embryos (E14). Voltage generated by spontaneous embryonic activity (motility) was measured on E15 to assess short-term effects of RIT; none were observed. There was no overall effect of these RIT doses on hatchability, though sample sizes were small (n = 13-15 per group). One to 2 weeks after hatching, chicks' acquisition of a detour learning response was tested. There were no observable effects of any RIT dose on detour learning. To assess potential effects of RIT on responsiveness to stress, some chicks were exposed to isolation stress approximately 3 weeks after hatching and killed 15 min later. Blood was assayed for serum corticosterone. There was no effect of any embryonic RIT dose on corticosterone concentrations in nonstressed subjects. Although corticosterone was elevated in all stressed groups, the group exposed to the highest embryonic RIT dose (2.7 mg/kg egg) showed a stress-induced elevation greater than other groups. Thus, except for the highest RIT dose (six to seven times greater than a therapeutically effective dose used in earlier work), embryonic RIT exposure on E14 had no effect on embryonic behavior, hatchability, posthatch learned behavior, and basal serum corticosterone concentrations. At a supraefficacious dose it appears to have modified the responsiveness of the neuroendocrine axis to mild stress.

Animals↗
PubMed1998

Open-field and LPS-induced sickness behavior in young chickens: effects of embryonic cocaine and/or ritanserin.

Exposure to drugs of abuse during embryogenesis may adversely affect nervous, immune, and endocrine systems development. We compared exposure on embryonic day 18 (E18) by single or multiple cocaine (COC) injections (56.25 mg/kg total dose for both) or saline on hatching and activity measures. In saline-exposed controls, repeated testing, age, and gender affected activity levels. A single or multiple COC injections increased the median latency to explore and multiple COC injections decreased the median number of lines crossed by female chicks in the open field. We also determined if pretreatment with the serotonin2 (5-HT2) receptor antagonist ritanserin could attenuate COC's effects on open-field behavior as well as behaviors sensitive to immune system stimulation (lipopolysaccharide (LPS)-induced sickness behavior). Eggs containing embryos were pretreated on E17 with 0.4 mg ritanserin/kg or its vehicle followed by multiple COC injections or saline on E18. E18 COC treatment decreased the median number of lines crossed and distress vocalizations in females. Ritanserin pretreatment mitigated the COC induced effects. E18 COC exposure also suppressed LPS-induced sickness behaviors in both males and females, increasing food consumption and the time spent awake and active, as well as decreasing the time spent sleeping. Ritanserin alone had no effect on the food consumed or time spent active, nor did this dose affect COC-induced alterations in sickness behavior. Ritanserin alone decreased time spent sleeping and also failed to affect the COC-induced suppression. Thus, embryonic COC exposure can suppress open field and LPS-induced sickness behavior in the young chick, and ritanserin pretreatment can block the former, but not the latter effects at the dose chosen for these experiments.

Animals↗
PubMed1997

Ontogeny of glucocorticoid receptors in the hyperstriatum-hippocampus-parahippocampal area and optic tectum of the embryonic chicken (Gallus domesticus) brain.

The importance of glucocorticoids and their perturbation during development is an active research area. Developmental insults, including direct and indirect consequences of exposure to drugs of abuse or withdrawal from them, may act upon or via the neuroendocrine axis of the pregnant experimental subject (e.g. rat) and/or directly upon the neuroendocrine axis of the embryo or fetus. The use of the domestic chicken embryo may constitute a good experimental subject for studying these effects in the absence of maternal influences. Thus, the pattern of brain glucocorticoid cytosolic receptors were characterized in an early developing brain region, the optic tectum (OT) and a later developing region with a different function, the hyperstriatum-hippocampus-parahippocampal (HHP) area, on embryonic days (E) 11, 15, 18 and on the day of hatching (HD). The influence of the glucocorticoid synthesis inhibitor metyrapone, injected into eggs on E14 and on E17, upon glucocorticoid receptors (on E15 and E18) was also studied to determine effects of a 'chemical adrenalectomy'. Receptors for this steroid are high on E11 and E15, decreasing as they approach the time of hatching, with the HHP generally showing greater numbers of specific binding sites for [3H]-corticosterone (CORT). Although metyrapone treatment did not alter the apparent number of receptors on E15, on E18 it unmasked receptors otherwise occupied by endogenous ligand(s) and/or induced their synthesis, resulting in significantly more receptors identified with [3H]-CORT. Nevertheless, the HHP continued to display more of these receptors than the OT on E15 and E18 after injection of metyrapone. These observations are consistent with the hypotheses that the HHP of embryos of this species contains a higher density of glucocorticoid receptors than does the OT; that glucocorticoid receptor quantification is related to steroid synthesis inhibition in late embryonic development; and that neuroendocrine feedback control of serum glucocorticoids may become functional between E15 and E18. The results also suggest the use of this experimental approach for assessing the effects of developmental insults with drugs, other than metyrapone, as a marker for altered neuroendocrine development and/or function.

Animals↗
PubMed1996

Excessive stimulation of serotonin2 (5-HT2) receptors during late development of chicken embryos causes decreased embryonic motility, interferes with hatching, and induces herniated umbilici.

The existence and functional significance of 5-HT2 receptors in chicken embryos was studied by injecting the selective agonist dimethoxyiodophenylaminopropane (DOI), alone or in conjunction with the selective 5-HT2 antagonist ritanserin (RIT), into domestic chicken eggs with embryos of varying ages. DOI caused dose-dependent reductions in hatchability and herniated umbilici in hatchlings. These effects were observed after injection early, mid, or late during embryonic development, with evidence of the toxic effects of DOI being greater in older embryos, probably due to 5-HT2 receptor activation late in development, even after injecting DOI as early as on day 3 of embryogenesis. This is based upon the fact that embryos in eggs injected with DOI early continued to develop apparently normally, failing to hatch, often after pipping their shells. Additionally, those that hatched often did so with herniated umbilici, as did late-exposed embryos, indicating that DOI's effects upon this organ were most likely mediated during the prehatching period (i.e., days 18-20). The agonist's selectivity was confirmed by the capacity of RIT to dose dependently block both of these toxic effects of DOI. Reduced embryonic motility monitored on day 19, after injection of DOI on the evening of day 18, suggests that excessive activation of 5-HT2 receptors late during development of this species interferes with some normal embryonic behaviors and physiological changes necessary for inducing and/or maintaining the hatching process.

Animals↗
PubMed1995

Potential efficacy and toxicity of GM1 ganglioside against trimethyltin-induced brain lesions in rats: comparison with protracted food restriction.

GM1 ganglioside (one week each at 10, 5, and 2.5 mg GM1/kg per day, ip) or gradual food restriction leading to a reduction in body weight to 75% of control were tested for their ability to block or reverse histopathologic and behavioral effects of trimethyltin (TMT) poisoning in rats. TMT (a single oral gavage of 6.0 mg TMT HCI/kg body weight) reduced hippocampal weight, decreased hippocampal cell counts, decreased autoshaped learning measures, and suppressed progressive fixed ratio (PFR) lever pressing without affecting stable lever pressing. Neither GM1 nor greater food restriction affected hippocampal weight. Greater food restriction prevented TMT's effects on autoshaping but not on PFR behavior, was without behavioral effects in animals not treated with TMT, and did not affect hippocampal histology. GM1 prevented certain TMT-induced decrements in autoshaping and PFR behavior but also suppressed autoshaping and stimulated stable fixed ratio behavior in animals not treated with TMT. GM1 also reduced hippocampal serotonin concentration, another "lesion-like" change. GM1 blocked TMT-induced hippocampal CA3b cell loss, but did not protect CA3c cells, the main locus of TMT hippocampal damage. The results support the idea that exogenous GM1 is a potent neuroactive agent with complex actions in intact organisms, potentially beneficial and potentially toxic. Like GM1, food restriction induces complex and potentially beneficial effects, but it lacked GM1's biochemical and behavioral "side effects" (i.e. toxicity) in these experiments.

Animals↗
PubMed1992

Interaction between mitogens upon intracellular Ca2+ pools in murine fibroblasts.

A comparison of the effect of platelet-derived growth factor (PDGF) and bombesin on intracellular Ca2+ stores was carried out in Swiss 3T3 cells loaded with Fura-2. It was found that the tumor promoter thapsigargin (Tg) almost completely inhibited both the PDGF- and the bombesin-induced intracellular Ca2+ concentration ([Ca2+]i) rise, indicating that the two mitogens mobilize Ca2+ from intracellular pool(s) sensitive to the tumor promoter. It was also found that pre-treatment with PDGF almost totally and persistently (up to at least 30 min) inhibited the bombesin-, Tg- and ionomycin-induced rise in [Ca2+]i, whereas pre-treatment with bombesin had only a partial inhibitory effect on the PDGF, Tg and ionomycin [Ca2+]i response, both in the absence and in the presence of external Ca2+. On the other hand, vasopressin and bradykinin, which also stimulate hydrolysis of phosphoinositides in these cells, did not affect the [Ca2+]i response induced by the same agents. These results indicate that, despite the poor production of inositol 1,4,5-trisphosphate (InsP3), PDGF was capable of totally discharging and maintaining discharged the InsP3-sensitive stores of intracellular Ca2+, regardless of whether extracellular Ca2+ was present in the medium. Bombesin only partially caused this effect. On the contrary, bradykinin and vasopressin, after releasing intracellular Ca2+ allowed an almost total refilling of the pools. It is interesting to note that, at variance with PDGF and bombesin, neither bradykinin nor vasopressin are able to induce a mitogenic response in Swiss 3T3 cells.

3T3 Cells↗
PubMed1992

Ganglioside treatment partially counteracts neurotoxic effects of trimethyltin but may itself cause neurotoxicity in rats: experimental results and a critical review.

We have demonstrated a deficit in working memory and/or consolidation of information in working memory into reference memory by a single oral dose of the neurotoxin trimethyltin(TMT). Moreover, TMT causes loss of hippocampal corticosterone receptors and increases brain glial fibrillary acidic protein(GFAP), an index of the astrocytic reaction to diverse types of CNS lesions. We tried to block the TMT-induced cognitive deficit and these biochemical markers by treating rats with purified mixed gangliosides (GS) for 21 days, starting 2 days before the TMT treatment. As expected, TMT decreased the number of corticosterone receptors in hippocampi and increased the GFAP concentration in hippocampi and to a lesser extent, in frontal cortices, measured more than 8 mon after treatment. The small increase in GFAP in frontal cortices was attenuated by GS but not in hippocampi. The pronounced learning deficits caused by TMT were attenuated to a small extent by GS in the TMT-GS group, when a learning criterion was used for the last session's performance of acquired lever-directed behavior. GS also delayed the appearance of significant performance differences between Controls and TMT-treated rats, when probed with a progressive fixed ratio schedule of reinforcement. However, most measures of learning and performance indicated that GS did not block the dysfunctional consequences of TMT treatment but instead caused similar functional decrements in rats treated with water instead of TMT. Corticosterone receptors in hippocampi were reduced to about 65% of Controls in the TMT-Water, TMT-GS, and Water-GS groups. A reduction in corticosterone receptors in hippocampi after TMT treatment probably reflects the loss of one or more cell types (e.g., pyramidal cells), which is supported by the increase in GFAP in this region. However, we did not observe a reciprocal relation between steroid receptors and GFAP after GS alone, indicating that GS did not cause detectable cell loss or cell damage, measured in this manner. Thus, reactive gliosis probably was not a pre-condition for the cognitive dysfunction. The fact that the cognitive deficits are probably related to hippocampal dysfunction supports the notion of a causal relationship between corticosterone receptor reduction and/or their altered function and cognitive impairment of this special type. The possibility that our results demonstrate potential neurobehavioral toxicity of GS is discussed in light of many reports which present data that can be similarly interpreted.

Animals↗
PubMed1991

Long-term effects of neonatal exposure to isobutylmethylxanthine. I. Retardation of learning with antagonism by mianserin.

Pregnant women regularly ingest the methylxanthines, caffeine and theophylline, during pregnancy and lactation. Also, theophylline is used to treat apnea in premature infants. In this study, rat pups were treated with 3-isobutyl-1-methylxanthine (IBMX), on days 7-10 of life. Transient IBMX treatment during infancy caused a retardation of acquisition of a delayed reinforced autoshaped lever touch response in adulthood. Treated rats required more trials to learn the task, but did not show altered exploratory activity in the operant chambers. Coadministration of the serotonin (5-HT) antagonist mianserin with IBMX was able to attenuate significantly the effects of IBMX in both males and females, even though mianserin treatment alone caused an apparent learning deficit in the males. The results indicate that 5-HT and 5-HT receptors are important during development for normal expression of a specific cognitive function later in life. Furthermore, a 5-HT system appears to play a role in the mechanism whereby perinatal methylxanthine exposure could lead to learning impairments or other undesirable behavioral consequences. The use of IBMX in developing rats may also offer a model for studying the long-term consequences of the expression of opioid withdrawal during the neonatal period, since this agent induces a quasi-morphine withdrawal syndrome (QMWS) in mature rats. It is of interest that mianserin can block or attenuate effects of both quasi- and true morphine withdrawal.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Long-term effects of neonatal exposure to isobutylmethylxanthine. II. Attenuation of acute morphine withdrawal in mature rats.

An acute model of morphine withdrawal was used to determine if neonatal exposure to 3-isobutyl-1-methylxanthine (IBMX) would cause alterations in the expression of withdrawal in the adult rat. IBMX induces a quasi-morphine withdrawal syndrome (QMWS), which is almost identical to true morphine withdrawal both behaviorally and neurochemically. Transient IBMX treatment during infancy (on days 7-10 of life) caused an attenuated suppression of fixed ratio (FR) responding during acute morphine withdrawal in adulthood; however, there appeared to be no attenuation of withdrawal-induced hypothermia. The attenuated behavioral response was not due to an altered ability to express withdrawal, as these rats did not react differently to various doses of IBMX plus naloxone (i.e., varying severities of quasi-morphine withdrawal) in adulthood. Coadministration of the serotonin (5-HT) antagonist mianserin with IBMX in the neonate prevented the effects of IBMX. Both the mianserin-treated and the IBMX plus mianserin-treated groups had increased levels of [3H]naloxone binding in brainstem, while IBMX treatment alone apparently had no significant effect. None of the neonatal drug treatments affected [3H]naloxone binding in frontal cortex. Thus, the long-term effects of IBMX on the opioid withdrawal response cannot be explained by changes in the number of opioid binding sites (labelled with [3H]naloxone) within the brain. The results indicate that exposure to a methylxanthine, and thus quasi-morphine withdrawal, during development results in long-lasting alterations of a system which is involved in opioid withdrawal. Because coadministration of mianserin prevented the effects of IBMX, 5-HT and 5-HT2 receptors are implicated in these effects.

1-Methyl-3-isobutylxanthine↗
PubMed1991

Acute opiate withdrawal in rats undernourished during infancy: impact of the undernutrition method.

Acute morphine withdrawal was assessed in adult rats following early postnatal undernutrition produced by two different methods (Large Litter procedure-20 pups/litter and Modified Slob procedure-rats cross-fostered on days 2, 4, and 6 to nonlactating dams for 24-hour periods). Response rates were first stabilized on a FR16 operant schedule. A single dose of morphine (20 mg/kg) was then administered, followed 4 h later by a single injection of naloxone (2.5 mg/kg). Males reared in large litters showed little behavioral disruption after morphine, suggesting either insensitivity to the opiate or the rapid development of tolerance. After naloxone. Modified Slob males displayed milder withdrawal than those in the well-nourished control or large litter groups. Thus the method of undernutrition influenced morphine's action and expression of withdrawal. A clear sex difference was also evident, females appearing to be generally less sensitive to the opiate- and naloxone-induced withdrawal than males. Body temperature underwent a characteristic elevation following morphine and a depression following naloxone across all groups, but undernutrition did not affect these responses. Hence, behavior proved to be the more sensitive measure for revealing differences in opiate dependence and withdrawal following early life undernutrition, under the test conditions employed.

Animals↗
PubMed1990

The serotonin2 antagonist ritanserin blocks quasi-morphine withdrawal at a time when mianserin is no longer effective.

A quasi-morphine withdrawal syndrome (QMWS), produced in opiate-naive rats with an injection of isobutylmethylxanthine (IBMX) and the opioid antagonist naloxone, allows one to study the expression of opiate withdrawal in the absence of the acute or chronic effects of opiates and the adaptive processes termed dependence. The allegedly selective and long-acting serotonin2 (5-HT2) antagonist ritanserin attenuated the QMWS-induced suppression of fixed ratio (FR) operant responding, which is a sensitive measure of the expression of a QMWS. When administered 30 min prior to precipitation of the QMWS, the lowest dose of ritanserin tested (0.158 mg/kg) was the most effective in blocking the expression of withdrawal; however, there was not complete reversal of the behavioral suppression. Acutely, the two higher doses of ritanserin tested (2.5 and 10 mg/kg) suppressed responding when given alone. This may have masked their ability to attenuate a QMWS. At a dose of 2.5 mg/kg, ritanserin completely blocked the QMWS-induced suppression of responding 24 h post-administration, at a time when its actions at other receptors (e.g., alpha 2) have dissipated. At an equivalent dose, the shorter-acting 5-HT2 antagonist mianserin was unable to attenuate the QMWS-induced suppression of FR operant responding 24 h post-administration. The 5-HT2 antagonists reportedly produce a paradoxical down-regulation of 5-HT2 binding sites upon chronic treatment, rather than the expected supersensitivity. Chronic treatment with ritanserin (2.5 mg/kg/day for 7 days), but not mianserin (same regimen), attenuated a QMWS 24 h after the final injection, thus supporting with a functional measure, the down-regulation of such binding sites by ritanserin.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1990

Delayed effects of amphetamine or phencyclidine: interaction of food deprivation, stress and dose.

Tritium-labelled phencyclidine (PCP) hydrochloride (12 mg/kg) was injected SC for six consecutive days into two groups of eight male rats maintained at 85% of their initial free-feeding weights. Eight days after the last injection, electric footshock raised fat levels of PCP 28% over nonshocked controls, and lowered blood levels 18%, but did not alter brain levels of the drug significantly. Thus, application of an acute stressor does result in redistribution of tissue stores of phencyclidine as predicted in the literature; however, the direction of the redistributions was to fat, rather than to brain. To explore the relation of a long-term stressor (one that eliminates adipose tissue as a sink for mobilized PCP), exploratory behavior was evaluated in male rats during six days of food deprivation commencing after six daily injections of PCP HCl (2 or 4 mg/kg, SC). Exploratory behavior of the 4 mg/kg dose group was abruptly altered, compared to saline controls, at six days of food deprivation, when the rats' body weights were about 70% of initial weights and when body fat would be severely reduced or depleted. To assess replicability and generalizability of this phenomenon, PCP HCl (4 or 8 mg/kg, SC) or dextroamphetamine sulfate (3.2 or 6.4 mg/kg, SC) was injected into male rats for six days and food deprivation followed afterward for nine consecutive days, or until similar body weight reductions as in the first experiment were achieved. Again, exploratory behavior was altered in comparison to saline controls in phencyclidine-treated rats (at the 4 mg/kg dose level) when rats reached about 70% of initial weights.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗