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S B Sparber

Publications and source records attributed to S B Sparber.

At least 55 records · Page 3Linked to original sources
PubMed1986

Ketanserin and pirenperone attenuate acute morphine withdrawal in rats.

The involvement of serotonin2 (5-HT2) receptors in the expression of opiate withdrawal was examined using a behavioral test for acute morphine dependence. The 5-HT2 antagonists, ketanserin and pirenperone, injected shortly before naloxone, attenuated the naloxone-induced suppression of an autoshaped lever-touch response in rats treated 4 h earlier with a moderate dose of morphine. A low dose of pirenperone was also effective in blocking withdrawal-induced hypothermia. These data support the hypothesis that 5-HT is involved in the expression of opiate withdrawal.

Animals↗
PubMed1986

Studies on the specificity of neurochemical and behavioral effects of LSD-25.

Brain perfusion experiments of conscious rats engaged in operant behavior and administered fluoxetine or LSD, with or without prior injection of 5-HTP, indicate there is probably more than one functional pool of 5-HT in the CNS. Furthermore, the fact that prior loading with the precursor is necessary before unmasking an effect of LSD suggests the LSD-sensitive pool is newly synthesized and represents only a small fraction of total CNS serotonin. Separating the effects of LSD's behavioral action into pausing (disruption) and depressed responding rate, with or without pausing, enabled us to demonstrate blockade of the disruption by methysergide without blockade of the decreased responding rate. Mianserin blocks both effects of LSD's action. We suggest that behavioral effects of low doses of LSD are due to sympathetic arousal and may offer a model for agitated depression and/or anxiety and that drugs of the mianserin-type may prove useful for treating some forms of anxiety, as well as depression.

Animals↗
PubMed1986

Mianserin attenuates naloxone-precipitated withdrawal signs in rats acutely or chronically dependent upon morphine.

The effects of the atypical antidepressant and serotonin antagonist mianserin on the expression of opiate withdrawal was examined using an acute and a chronic model of morphine dependence. In the first experiment, rats, trained to perform a food-reinforced, autoshaped lever touch response, were injected with naloxone (5 mg/kg) 4 hr after treatment with a single moderate dose of morphine (15 mg/kg). Mianserin (0.25, 1.0 and 2.5 mg/kg) attenuated the naloxone-induced suppression of autoshaped responding. Colonic temperatures were also monitored. Morphine treatment resulted in significant hyperthermia, while precipitation of withdrawal by naloxone produced hypothermia. Mianserin also attenuated the naloxone-induced hypothermia. In the second experiment, rats were implanted s.c. with a single 75-mg morphine or placebo pellet. Withdrawal was precipitated with naloxone (5 mg/kg) 24, 48 and 120 hr post implantation. Mianserin (2.5 mg/kg) blocked or attenuated signs of withdrawal precipitated by naloxone. Naloxone-precipitated weight loss was also attenuated 48 and 120 hr post implantation. At 120 hr post implantation, rats were decapitated 1 hr after the administration of naloxone and trunk blood was collected. Mianserin did not block the naloxone-induced rise in plasma corticosterone levels. Thus, several signs of withdrawal (e.g., behavioral effects, weight loss and hypothermia) seem to involve serotonergic mediation and can be blocked by mianserin, while others (e.g., rise in plasma corticosterone), which may be unaffected by mianserin, may be a reflection of a compensatory response to withdrawal stress, rather than a mediator of maladaptive consequences of withdrawal that are not mediated by serotonin.

Animals↗
PubMed1985

Behaviorally equivalent stressors differentially modify the monoamine altering property of d-amphetamine.

We previously demonstrated that behaviorally equivalent heat and cold stressors interacted with d-amphetamine (AMPH) treatment to produce different effects in rats responding for food on a fixed ratio 15 (FR15) schedule of reinforcement [25]. The present study was carried out to determine if these stressors differentially affect the disposition of AMPH to brain and/or if the stressors alone or in combination with AMPH affect CNS monoamines in a dissimilar manner. Exposure to either heat or cold stressor produced equivalent elevations of [3H]-AMPH in brain following 3 mg AMPH/kg but not 1 mg AMPH/kg. Neither stressor alone significantly altered any of the neurochemical parameters measured in any of the brain regions studied. In forebrain, heat and cold stressors interacted with AMPH treatment in different manners. Thus, although [3H]-AMPH was equally elevated in stressed groups following the high dose, cold-induced stress was not associated with an increase in dopamine (DA) levels, which was observed in Nonstressed and Heat-Stressed subjects. Although serotonin (5-HT) levels were not changed by any manipulation, 5-hydroxyindoleacetic acid (5-HIAA) levels were lowered in Nonstressed and Cold-Stressed subjects following both doses of AMPH. This effect was not associated with heat-induced stress. The apparent attenuation of AMPH behavioral toxicity observed in Cold-Stressed and/or exacerbation in Heat-Stressed rats observed in the earlier study may involve a pharmacodynamic interaction of AMPH and stress with transmitter substances, including DA and/or 5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Indomethacin facilitates acute tolerance to and dependence upon morphine as measured by changes in fixed-ratio behavior and rectal temperature in rats.

The effects of indomethacin, a prostaglandin (PG) synthetase inhibitor, on acute tolerance to and dependence on morphine were investigated. Twelve mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and have their rectal temperature taken. The experimental protocol began with taking the rat's temperature followed by a 30 minute behavioral session. Immediately after this session the animal was injected with indomethacin or its vehicle. Two-and-a-half hours later this procedure was repeated, except that morphine or saline was administered. After an additional 2.5 hours had elapsed, a 60 minute behavioral session occurred. Half-way through the session the rat was injected with morphine (tolerance), naloxone (dependence), or saline. Immediately after the session the rat's temperature was recorded. Indomethacin potentiated the acute tolerance to the behavioral suppressant and hyperthermic effects of morphine. Indomethacin pretreatment also greatly enhanced the capacity of naloxone to decrease temperature and suppress FR 30 behavior in morphine-treated rats. These effects were not due to indomethacin altering the acute effects of morphine or the amount of morphine in the brain. These data suggest that indomethacin is inhibiting synthesis of PGs which are important in morphine tolerance and dependence.

Animals↗
PubMed1985

Central administration of prostaglandin E2 facilitates while F2 alpha attenuates acute dependence upon morphine rats.

The effects of prostaglandin D2 (PGD2), E2 (PGE2), and F2 alpha (PGF2 alpha) on acute dependence on morphine were investigated. Five mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and implanted with permanent guide cannulas with the tips of the cannulas in their right lateral brain ventricles. The experimental protocol began with a 45 minute behavioral session and brain infusion (1 microliter/minute of a solution containing 2.3 mM CaCl2 in 0.9% saline, ICV). Fifteen minutes into the session the rats were injected with 7.5 mg morphine/kg (IP). Beginning 2.25 hours later the brain infusion was reinitiated during a second 45 minute behavioral session which was interrupted after 15 minutes to inject 1.0 mg naloxone/kg (IP). In several experiments a dose of PG, which did not in-and-of-itself affect behavior, was added to the infusion medium. Prior to the naloxone injection it was ascertained that the behavioral effects of morphine had dissipated. The injection of naloxone or saline did not alter behavior of the rats while they were being infused with a PG or PG vehicle. Injection of naloxone, 3 hours after the injection of morphine, resulted in a significant suppression of FR 30 behavior (withdrawal). A dose of PGE2, which did not alter the initial suppressant action of morphine, potentiated the naloxone effect. A dose of PGF2 alpha, which likewise did not alter the initial action of morphine, antagonized the naloxone effect. However, a higher dose of PGF2 alpha which enhanced the initial morphine effect, caused an enhanced naloxone effect as well.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Greater task difficulty amplifies the facilitatory effect of des-glycinamide arginine vasopressin on appetitively motivated learning.

Rats were trained in a discrete-trial forward autoshaping paradigm to touch an extended lever to earn food pellets. Reinforcement was delivered either simultaneously with or 6 s after lever retraction which occurred either non-contingently after 15 s or when the animal touched the lever. Treatment with des-glycinamide arginine vasopressin (DGAVP; 15 micrograms/kg, sc) 1 hr before sessions increased the rate of acquisition of the extended-lever-touch response and also facilitated development of intertrial (adjunctive) nose poking. Effects of the peptide were more robust in the more difficult, delayed reinforcement task. DGAVP lacks the classical peripheral activity of vasopressin. In both experiments, peptide treatment was terminated before asymptotic levels of performance were attained; the continued facilitation of acquisition in treated groups suggests a specific enhancement of learning and/or enhanced memory retrieval.

Animals↗
PubMed1985

Long lasting behavioral effects of dimethyl sulfoxide and the "peripheral" toxicant p-bromophenylacetylurea.

Behavioral toxic effects caused by a relatively small dose of the "peripheral" neurotoxin, p-bromophenylacetylurea (BPAU), and of its vehicle, dimethyl sulfoxide (DMSO) were investigated. BPAU induces, in rats, a central-peripheral distal axonopathy similar to that produced in humans by toxic organophosphorus-containing compounds, and has been proposed as a model to study this type of toxicity in a convenient experimental mammal. Rats were injected with BPAU (50 or 100 mg/kg) in DMSO (1 ml/kg), with DMSO alone, or with saline. 100 mg BPAU/kg produced permanent weight loss and hind limb paresis; the low dose did not. Behavioral testing, 2 days to 4 mo post-treatment, indicated that DMSO and/or 50 mg/kg of BPAU retarded habituation of spontaneous exploratory activity, impaired acquisition of conditioned (auto-shaped) behavior, and changed the dose-response relationship ford-amphetamine-induced suppression of operant (fixed ratio 32) responding. BPAU-treated animals were also impaired in initial performance of operant behavior maintained by a fixed ratio schedule of reinforcement, at high (greater than or equal to FR 16) ratio values. Thus, neurobehavioral toxicity may occur at doses too low to induce organophosphorus-type sensorimotor impairment or pathology. Further, DMSO may also exert effects on neurobehavioral function, suggesting it too may be potentially toxic within this domain.

Animals↗
PubMed1984

Neonatal opiate withdrawal alters the reactivity of adult rats to the hot-plate.

Prenatal exposure of rats to 0.2 mg LAAM/kg/day but not to 0.05 mg LAAM/kg/day resulted in faster hot-plate escape latencies in 6 mo old offspring. No differences in tail-flick latencies were observed at 7 mo of age in offspring exposed to either dose of LAAM prenatally. Subsequent testing of littermates at 16 mo of age revealed that the greater sensitivity to the hot-plate observed in rats prenatally exposed to LAAM is apparently a result of neonatal withdrawal rather than a primary consequence of the drug. The data are discussed in relation to possible effects of drug or withdrawal on central nervous system development.

Animals↗
PubMed1984

Indomethacin potentiates the operant behavior suppressant and rectal temperature lowering effects of low doses of d-amphetamine in rats.

Prostaglandins (PGs) may be important in modulating the actions of d-amphetamine. To test this hypothesis male rats were pretreated with indomethacin to inhibit PG synthesis before d-amphetamine was injected. Indomethacin (5 mg/kg, IP) was found to be without direct effect upon fixed-ratio behavior or rectal temperature, but significantly enhanced the capacity of low doses of d-amphetamine to suppress behavior and lower temperature. These effects were not due to partial food deprivation or to an increase in the concentration of d-amphetamine in brain. It is concluded that one or more of the PGs modulate the central actions of d-amphetamine, perhaps by modifying the release and/or reuptake of catecholamines, or through a postsynaptic action.

Animals↗
PubMed1984

Amphetamine cumulation and tolerance development: concurrent and opposing phenomena.

Whether diminished or augmented behavioral effects are observed after repeated amphetamine administration may reflect the relative balance between tolerance and drug cumulation. To investigate this, we measured the distribution of d-amphetamine in various tissues and its effects on performance of a conditioned behavior after acute or chronic treatment. Rats trained to lever press under a fixed ratio 5 schedule for food-reinforcement were tested daily for 4 min epochs in each of 6 consecutive hours. After responding was stable, animals were injected for 16 days with saline or 1.0, 2.5 or 5.0 mg 3H-d-amphetamine sulfate/kg IP 15 min before the second daily behavioral epoch. On the 17th day, animals which had been receiving 3H-d-amphetamine were given their usual dose and those which had been receiving saline were given one of the doses of 3H-d-amphetamine; all animals were decapitated approximately 2 1/4 hours after this final injection, immediately after the 4th behavioral epoch. Brain, heart, muscle, epididymal fat, and kidney were removed for subsequent analysis of unchanged 3H-d-amphetamine. The experiment was carried out in two phases, 3 1/2 months apart, which inadvertently resulted in shipment of rats from different buildings on the supplier's campus. Acute treatment produced dose-related effects on operant responding, the lowest dose increasing responding and the highest dose suppressing it. Chronic injection of the highest dose of d-amphetamine resulted in significant attenuation of its acute suppressant effect. Additionally, chronic treatment suppressed responding of rats 23 1/4 hours after injection (i.e., before the subsequent daily injection). Tissue levels of d-amphetamine were dose related and d-amphetamine cumulated after chronic treatment with the highest dose. When d-amphetamine was administered acutely, the behavioural effect immediately before decapitation was highly correlated with the concentration of d-amphetamine in brain and in heart. This was not the case after chronic treatment, since rats given the higher doses showed less behavioural effect than would have been predicted from the concentrations of d-amphetamine in their tissues. Besides evidence of tolerance and cumulation of drug in one or more tissues, a significant phase or colony difference emerged, which could have been due to seasonal or other factors. Additional, different experiments, performed concurrently on a new shipment of rats from each colony, allowed us to conclude that the original observations of phase differences were not due to seasonal differences or chance.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

d-Amphetamine antagonizes prostaglandin E1-induced hyperthermia and suppression of fixed interval operant behavior in rats.

The experiments reported herein were designed to study the effects of prostaglandin F2 alpha (PGF2 alpha) and PGE1 on operant behavior and rectal temperature of rats. A solution containing PGF2 alpha or PGE1 was infused intracerebroventricularly into rats trained to press a lever for food reward on a fixed interval 75 second (FI 75 sec) schedule. PGF2 alpha (10, 100 or 1000 ng/min) had no effect on FI 75 sec operant behavior. Only the highest dose increased temperature. PGE1 (100 ng/min) had no effect, whereas higher doses (250 and 500 ng/min) produced a rate-dependent effect on behavior, increasing low rates and decreasing high rates. The two higher doses also produced convulsions after about 25 min or 20 min infusions, respectively. PGE1 also increased temperature in a dose-dependent manner. Systemic administration of a low dose of d-amphetamine (0.5 mg/kg IP) had little or no effect on behavior or temperature. d-Amphetamine did not alter hyperthermia induced by the highest dose of PGF2 alpha, but antagonized the PGE1-induced hyperthermia. d-Amphetamine also antagonized all of the behavioral effects of PGE1, including convulsions. The results are discussed in relation to the actions of PGs and d-amphetamine on catecholamine neurons in the central nervous system.

Alprostadil↗
PubMed1984

A comparative study of the effects of prostaglandins and d-amphetamine on the metabolism of 3H-dopamine continuously presented to rat brain in vivo.

Unanesthetized rats with chronic indwelling cannulas, engaged in food reinforced operant behavior, were infused intracerebroventricularly with a solution containing a trace concentration of 3H-dopamine (3H-DA) with or without prostaglandins (PGs). Approximately 45 minutes after the infusion was started, the procedure was changed to a push-pull perfusion. Perfusate from the ventricles contained significant quantities of the 3H-DA metabolites 3H-3,4-dihydroxyphenylacetic acid (3H-DOPAC), 3H-3-methoxy-4-hydroxyphenylacetic acid (3H-homovanillic acid, 3H-HVA), 3H-3-methoxytyramine (3H-3-MT), and the 3H-noradrenaline (3H-NA) metabolite 3H-3-methoxy-4-hydroxy-phenylethyleneglycol (3H-MHPG). The presence of PGF2 alpha decreased the amount of 3H-DOPAC, 3H-HVA, and 3H-3-MT in perfusate, while PGE1 had the opposite effects. d-Amphetamine (0.5 mg/kg, 1P) affected the recovery of these metabolites from perfusate in a manner similar to PGF2 alpha and opposite to PGE1. PGF2 alpha and the highest (seizure-inducing) dose of PGE1 significantly decreased, while d-amphetamine significantly increased, the quantity of 3H-MHPG in perfusate. Therefore, PGs affect central dopaminergic and noradrenergic activity in vivo, as reflected by changes in their metabolic profiles, and may play a role in the response of the central nervous system to drugs which act through catecholaminergic mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1984

A kindling-like effect induced by repeated exposure to heated water in rats.

Hyperthermia was induced in mature rats by immersing them in 20 cm of 45 degrees C water for 4 min. Rats were made hyperthermic once every 4 days for six exposures. A significant number had at least one convulsion by the third exposure. During the seventh exposure, 2 weeks after the sixth exposure, twice as many rats experienced convulsions. Two weeks later, four rats that had convulsed following exposure to heated water at an earlier time convulsed on exposure to a strobe light flashing at 25 Hz. The percentage of rats having experienced at least one convulsion increased dramatically when tested 2 and then an additional 3 months later. Spontaneous (handling-induced) convulsions also occurred in a few rats that had been exposed to heated water previously. The data indicate that repeated exposure to this type of hyperthermia can result in an increase in convulsive susceptibility in mature rats and may be a useful, noninvasive model for studying kindling, febrile convulsions, and epilepsy in rodents.

Animals↗
PubMed1983

Separation of hepatic N-demethylase-inducing and opioid dependence-producing doses of levo-alpha-acetylmethadol in the pregnant rat.

A 2.0 mg per kg oral dose of 1-alpha-acetylmethadol (LAAM) administered daily to female rats prior to mating and throughout pregnancy increased ethylmorphine N-demethylase activity in liver microsomes of the dams measured 24 h after parturition. This dose of LAAM decreased maternal weight gain during gestation and increased postnatal mortality. However, 0.05 mg LAAM per kg was sufficient to produce dependence in the dams without affecting hepatic drug metabolism, gestational weight gain or neonatal mortality. The data indicate that it is not necessary to use doses of LAAM which can affect drug metabolizing enzymes in dams and increase pup mortality to maintain opioid-type physical dependence.

Animals↗
PubMed1983

Postnatal abstinence or acute toxicity can account for morbidity in developmental studies with opiates.

The incidence of neonatal morbidity and mortality in rats exposed to opiates in utero is generally high. To determine the extent to which neonatal opioid intoxication and/or withdrawal contribute to this effect, addicted pups from dams treated chronically with the long-acting opioid levo-alpha-acetylmethadol (LAAM) and appropriate controls were injected within 12 h of birth with saline, an opioid agonist (LAAM and metabolites) or an antagonist (naloxone). The incidence of neonatal mortality for pups born to dams maintained on a high dose of LAAM was 52%. A single injection of agonist on the first day of life reduced mortality in this group to 29% while a single injection of the antagonist increased mortality to 88%. In contrast, administration of the agonist to control pups and pups born to dams maintained on lower doses of LAAM resulted in increased mortality. Naloxone was apparently innocuous in non-dependent neonates. These data show that, despite LAAM's long duration of action in the mature rat, newborn rats experience withdrawal soon after drug exposure is terminated. These data also indicate that continued opioid exposure is a highly effective means of treating/preventing severe spontaneous withdrawal in the newborn.

Animals↗