Role of monoamine oxidase type A and B on the dopamine metabolism in discrete regions of the primate brain

The role of monoamine oxidase (MAO) type A and B on the metabolism of dopamine (DA) in discrete regions of the monkey brain was studied. Monkeys were administered (-)-deprenyl (0.25 mg/kg) or clorgyline (1.0 mg/kg) or deprenyl and clorgyline together by intramuscular injections for 8 days. Levels of DA and its metabolites, dihydroxy phenylacetic acid (DOPAC) and homovanillic acid (HVA) were estimated in frontal cortex (FC), motor cortex (MC), occipital cortex (OC), entorhinal cortex (EC), hippocampus (HI), hypothalamus (HY), caudate nucleus (CN), globus pallidus (GP) and substantia nigra (SN). (-)-Deprenyl administration significantly increased DA levels in FC, HY, CN, GP and SN (39-87%). This was accompanied by a reduction in the levels of DOPAC (37-66%) and HVA (27-79%). Clorgyline administration resulted in MAO-A inhibition by more than 87% but failed to increase DA levels in any of the brain regions studied. Combined treatment of (-)-deprenyl and clorgyline inhibited both types of MAO by more than 90% and DA levels were increased (57-245%) in all brain regions studied with a corresponding decrease in the DOPAC (49-83%) and HVA (54-88%) levels. Our results suggest that DA is metabolized preferentially, if not exclusively by MAO-B in some regions of the monkey brain.     

Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions.

[Correction Notice: An erratum for this article was reported in Vol 107(2) of Behavioral Neuroscience (see record 2008-10474-001). Table 1, on page 119, contains two errors. In the first section, the dose/route for the agent nicotine should read as follows: 1.2-2.0 mg/kg sc. In the second section, the dose/route for the agent morphine should read as follows: 2-80 mg/kg ip. Also, on page 121, paragraph 3, line 14, the parenthetical information after 40 mg/kg cocaine should read (40C; 2 × 20 mg/kg/3 cc).] The nature of flavor–drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg, sc), phencyclidine (0.5, 2, 10, or 20 mg/kg, sc), and methamphetamine (2, 5, or 10 mg/kg, ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. Results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

"Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions": Correction to Parker.

Reports an error in "Taste reactivity responses elicited by cocaine-, phencyclidine-, and methamphetamine-paired sucrose solutions" by Linda A. Parker (Behavioral Neuroscience, 1993[Feb], Vol 107[1], 118-129). Table 1, on page 119, contains two errors. In the first section, the dose/route for the agent nicotine should read as follows: 1.2-2.0 mg/kg sc. In the second section, the dose/route for the agent morphine should read as follows: 2-80 mg/kg ip. Also, on page 121, paragraph 3, line 14, the parenthetical information after 40 mg/kg cocaine should read (40C; 2 × 20 mg/kg/3 cc). (The following abstract of the original article appeared in record 1993-24959-001.) The nature of flavor–drug associations produced by a range of doses of the reinforcing agents cocaine (5, 10, 15, 20, or 40 mg/kg, sc), phencyclidine (0.5, 2, 10, or 20 mg/kg, sc), and methamphetamine (2, 5, or 10 mg/kg, ip) were assessed by the taste reactivity (TR) test and the conditioned taste avoidance (CTA) test. Even at the highest doses tested, none of the agents produced aversive TR responding. At doses that produced equivalent-strength CTA, lithium did establish aversive TR responding. Results provide evidence that drugs that serve as reinforcers in other paradigms produce conditioned flavor avoidance that is not motivated by a conditioned dislike for the flavor. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spontaneous and drug-stimulated locomotor activity after the administration of pertussis toxin into the ventral tegmental area

Pertussis toxin (PTX) injected into the ventral tegmental area (VTA) produces an enhanced locomotor response to amphetamine. In the present study, we have evaluated the role of dopamine receptors on spontaneous locomotor activity and the enhanced locomotor response to dopaminergic agonists after the administration of PTX into the VTA. PTX injected into the VTA of rats produced a delayed increase in spontaneous locomotor activity with a latency of 4 d. This activity was markedly increased by day 6 and remained elevated for at least 28 d after PTX treatment. This increased spontaneous locomotor activity of PTX-treated animals was antagonized by the administration of the D1 receptor antagonist SCH23390 (0.03 and 0.1 mg/kg sc), but not by the D2 receptor antagonist eticlopride (0.1 and 0.3 mg/kg sc). After adaptation to the locomotor cages, the animals showed a markedly enhanced motor response to amphetamine (0.5 mg/kg ip) and apomorphine (5 mg/kg sc). The heightened locomotor responses to these dopaminergic agonists could be elicited for at least 2 mo after PTX administration. The enhanced response to amphetamine was antagonized by the administration of SCH23390 (0.03 and 0.1 mg/kg sc), but not by eticlopride (0.1 mg/kg). The increased response to apomorphine in PTX-treated animals was inhibited by SCH23390 (0.1 mg/kg sc) and partially inhibited by eticlopride (0.1 mg/kg sc). Both of these antagonists inhibited the spontaneous and the drug-induced locomotor responses in vehicle-treated control animals. These results suggest that the administration of PTX into the VTA leads to an increase in spontaneous and drug-induced locomotor activity in which D1 receptors seem to play an important role.     

Acute effects of pentobarbital in a monkey operant behavioral test battery

The effects of acute pentobarbital treatment were assessed using a complex operant test battery containing five tasks in which correct performance is thought to depend upon processes associated with short-term memory and attention [delayed-matching-to-sample (DMTS)], color and position discrimination [conditioned position responding (CPR)], motivation [progressive ratio (PR)], time perception [temporal response differentiation (TRD)], and learning [incremental repeated acquisition (IRA)]. Adult, male rhesus monkeys were tested 15 min after IV injection of saline or pentobarbital (1, 3, 5.6, 10, or 15 mg/kg). Behavioral endpoints measured included percent task completed, response rate or latency, and response accuracy. The order of task sensitivity to disruption by PBT was TRD > IRA = DMTS = PR > CPR, in which sensitivity was defined as a significant disruption in any aspect of task performance. PBT slowed response rates at 10.0 and/or 15.0 mg/kg in all tasks. Accuracy was decreased in the TRD task at > or = 5.6 mg/kg but doses of > or = 10.0 mg/kg were required to decrease accuracy in the IRA, DMTS, and CPR tasks. Thus, behavior thought to model time perception (TRD) was more sensitive than behavior modeling learning (IRA), short-term memory and attention (DMTS), and motivation (PR). CPR was the least sensitive behavior. Because pentobarbital exerts its effects at least in part via GABA systems, the effects in the current study were compared with those of a previous study of the acute effects of diazepam. The two compounds exerted fundamentally different effects on operant test battery performance.     

Inhibition of platelet aggregation by acetylsalicylic acid and other inhibitors

Effects on platelet aggregation were examined of acetylsalicylic acid (ASA), indomethacin and a number of other agents including dipyridamole, phenylbutazone and sulfinpyrazone under standardized conditions. The Born turbidometric method of measuring platelet aggregation was used with collagen as the stimulus for aggregation. ASA and indomethacin were shown to be among the most potent inhibitors of aggregation, being active at minimal effective concentrations of 1-3 mug/ml using a 10 min time of pre-incubation with the platelet-rich plasma (degree of aggregation inhibition was time dependent). Most of the other agents tested were also active in vitro and both prostaglandin E1 and adenosine were more potent than ASA or indomethacin. However, these agents were shown not to exert significant inhibitory effects when administered orally to rats (dose 10 and 30 mg/kg). ASA proved to be effective in doses as low as 3 mg/kg, and indomethacin in doses as low as 1 mg/kg orally. The inhibitory effects of ASA on aggregation remained for several days after a single oral dose, whereas the effects of indomethacin disappeared within 24 h.     

The toxicity of IDPN on the vestibular system of the rat: new insights on its effects on behavior and neurofilament transport

3,3'-Iminodipropionitrile (IDPN) causes a permanent syndrome of abnormalities in spontaneous behavior and a deficit in the axonal transport of neurofilaments (NF). Male Long-Evans rats were given IDPN (0, 200, 400, 600, or 1000 mg/kg, ip, in saline) and assessed for behaviors indicative of vestibular function at 1 week post-dosing. The morphology of the peripheral vestibular system in animals dosed with 0, 200, 400, 600, 800, or 1000 mg/kg of IDPN was assessed at 4 days post-dosing by light microscopy on semithin sections. Animals receiving 1000, 1500, or 2000 mg/kg of IDPN were assessed for morphological alterations in the vestibular ganglion at 8 days post-dosing. Behavioral data indicated a dose-dependent loss of vestibular function after IDPN, the vestibular deficits first appearing at the 400 mg/kg dose level. IDPN exposure was also observed to result in degeneration of the vestibular sensory hair cells. Degenerative changes were already found at the 400 mg/kg dose level, and were extensive after 1000 mg/kg. In the ganglion neurons, no effects were observed after 1000 mg/kg of IDPN, but perikaryal accumulations of NF were found after 1500 or 2000 mg/kg. In conclusion, the data showed that low doses of IDPN are toxic to the vestibular hair cells, and suggest a link between this action and the effects of the chemical on spontaneous behavior. In addition, doses of IDPN larger than those required for toxicity to the vestibular sensory cells, induced accumulations of NF in the myelinated cell bodies of the vestibular ganglion neurons.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of infant colic on maternal self-perceptions and mother-infant attachment

The 5-HT2A and 5-HT2C antagonists MDL 100,907 and SER-082 were tested with the 5-HT2A/C agonist DOI and the 5-HT1A/2A/2C agonist LSD in the Behavioral Pattern Monitor, which provides multiple measures of locomotor and investigatory activity. Previous investigations have shown that these measures load onto three independent behavioral factors: amount of activity, exploratory behavior, and behavioral organization. Rats pretreated with saline, MDL 100,907 (0.25-2.0 mg/kg), or SER-082 (0.5-1.0 mg/kg) were treated with saline, 0.25 mg/kg DOI, or 60 micrograms/kg LSD. All effects of DOI were blocked by all doses of MDL 100,907, but only by the highest dose of SER-082. While the effects of LSD on activity and exploratory behavior were largely unaffected, either pretreatment antagonized the effects of LSD on behavioral organization. Thus, all of these effects of DOI were attributable to 5-HT2A receptors, whereas the effect of LSD on behavioral organization was influenced by both 5-HT2A and 5-HT2C receptors.     

Interactive effects of prenatal cocaine and nicotine exposure on maternal toxicity, postnatal development and behavior in the rat

Two experiments were performed to investigate the interactive effects of prenatal coadministration of cocaine hydrochloride (C) and nicotine tartrate (N). Experiment I was designed to determine doses of C and N that could be coadministered without altering maternal gestational parameters and/or fetal viability. Exposure of Sprague-Dawley rats to combined high-dose C (20 mg/kg) and high-dose N (5.0 mg/kg) on gestation days 8-21 was not more toxic to dam or fetus that that of exposure to C alone. Experiment II investigated pregnancy outcome, postnatal development, and behavior of the offspring following drug exposure to either high-dose cocaine (20 mg/kg: CS), high-dose nicotine (5.0 mg/kg: NS), or both (NC) on gestation days 8-21. N was administered by osmotic minipump and C by sc injection. Saline-injected dams, fitted with saline-fitted pumps (SS), and untreated dams, pair-fed (PF) to NC females, served as controls. Alterations in maternal variables were limited to a 10-15% decrease in food consumption in NC and CS groups. Pregnancy outcome and birth statistics were unaffected by prenatal treatment, as was offspring body weight during the first four postnatal weeks. However, the development of surface righting was delayed inC CS pups, and only CS offspring were underresponsive to the stimulatory effects of dopamine agonists on activity and stereotypy. Behavioral responses to N challenge were similar in all groups. In addition, only CS offspring showed altered behavioral responses in a spontaneous alternation task. Treatment effects on dopamine D1 and D2 binding in the caudate nucleus were not observed. The combination of N and C did not exacerbate any of the behavioral changes seen in CS offspring. These results support the hypothesis that C is a behavioral teratogen in rodents, and suggest that in the present model, nicotine can mitigate some of the consequences of in utero exposure to cocaine.     

Delayed development of symptomatic improvement by (--)-deprenyl in Parkinson's disease

Twenty de novo patients with Parkinson's disease (Hoehn-Yahr stages I, II, III) were studied in a double blind trial after introducing (--)-deprenyl monotherapy. The parkinsonian symptoms were assessed by a novel graded clinical rating scale, by UPDRS and by the North Western self-rating scale. A significant change was observed in motor behaviour and daily activity (UPDRS) after 3 weeks of treatment with (--)-deprenyl at 10 mg/day. The total scores using UPDRS and the North Western ratings were changed significantly after 4 weeks. The greatest changes observed were in walking and in hypokinesia. Rigidity was not modified by (--)-deprenyl.     

Behavioral assessment of neuroleptics (3)--Schizophrenia negative symptoms-like model induced by PCP

Immobility induced by forced swimming is well known as an animal model of depression. To develop an animal model for the negative symptoms of schizophrenia, in particular, the depressive symptoms, the effect of phencyclidine (PCP) on immobility in the forced swimming test was investigated in mice, since PCP produces negative symptoms-like behavioral changes in humans. Repeated treatment with PCP (10 mg/kg/day, sc, once a day for 14 days) prolonged the immobility time in the forced swimming test 24 hr after the final injection compared with saline treatment; the effect was not obtained by single treatment with PCP (10 mg/kg), or by repeated treatment with methamphetamine (0.3 and 1 mg/kg/day, sc, once a day for 14 days). The enhancing effect of PCP on the immobility persisted for at least 21 days after the withdrawal of the drug. Desipramine (10 mg/kg, po) attenuated the immobility induced by the forced swimming in mice repeatedly treated with saline. The enhancing effect of PCP on the immobility was attenuated by risperidone (0.3 mg/kg), clozapine (3 and 10 mg/kg), and desipramine (20 and 50 mg/kg), whereas haloperidol (0.3 and 1 mg/kg) had no effect. These results suggest that the enhancement of immobility in the forced swimming test brought about by repeated PCP treatment could be used as a model of the negative symptoms, particularly the depression, of schizophrenia.     

Dexmedetomidine, diazepam, and propranolol in the treatment of ethanol withdrawal symptoms in the rat

In this study, the effects of dexmedetomidine, a selective alpha 2-adrenoceptor agonist, on ethanol withdrawal symptoms, were compared with those of diazepam and propranolol. The rats were given highly intoxicating doses of ethanol for 4 days. After the intoxication period, rats were divided into four equal groups: a dexmedetomidine-treated group (30 micrograms/kg, sc), a diazepam-treated group (2 mg/kg, sc), a propranolol-treated group (5 mg/kg, sc), and a control group with no medication. Medication was given in the withdrawal phase-2, 8, 14, and 20 hr after the onset of the withdrawal symptoms. The severity of the ethanol withdrawal symptoms (rigidity, tremor, irritability, and hypoactivity) was observed up to 33 hr after the onset of the ethanol withdrawal symptoms. Both dexmedetomidine and diazepam significantly relieved tremor compared with the control group. Diazepam reduced irritability significantly, compared with the control group. When measured as the sum score of the three most specific withdrawal signs (rigidity, tremor, and irritability), dexmedetomidine and diazepam significantly relieved the ethanol withdrawal reaction. Propranolol attenuated tremor, but was inefficient against other withdrawal symptoms. Dexmedetomidine may thus represent a new effective drug in the treatment of the ethanol withdrawal syndrome.     

Morphine influences on classical aversive conditioned heart rate in rats.

Investigated in 3 experiments the effects of morphine and the morphine antagonist naloxone on the development of a classical aversive heart rate (HR) conditioned response (CR) to a tone conditioned stimulus (CS) paired with an electric shock unconditioned stimulus (US). In Exp I, groups of rats received either 0.25, 5 or 10 mg/kg, sc, of morphine. Three other groups were given 0.1, 5, or 10 mg/kg of naloxone. All morphine groups showed attenuation HR responses to the CS on preconditioning CS-alone trials. During conditioning, the 10-mg/kg morphine group showed a markedly decremented bradycardia CR and tachycardia unconditioned response (UR), whereas the 5-mg/kg morphine group showed a normal CR in combination with a decremented UR. In the Exp II, 1 mg/kg naloxone given after conditioning failed to reverse the CR and UR losses produced by 10 mg/kg of morphine given prior to conditioning. 10 mg/kg of morphine produced only a minor reduction in a HR CR established in a drug-free state, but the tachycardia UR was severely reduced. Exp III showed that 1 mg/kg of naloxone was effective in reversing analgesia induced by 10 mg/kg of morphine. 10 mg/kg dose of morphine interfered with the learning of a HR CR, perhaps principally by reducing the aversive or emotional consequences of the shock US. Direct cardiovascular effects of morphine seemed to interfere with the performance of the tachycardia UR, but not with the performance of the bradycardia CR. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of interleukin-1 receptor antagonist in a slow-release hylan vehicle on rat type II collagen arthritis

PURPOSE: To determine the effect of hylan fluid (HA), a model slow release vehicle on the pharmacokinetic profile and efficacy of interleukin-1 receptor antagonist (IL-1ra) in rats with established type II collagen arthritis. METHODS: Female Lewis rats with type II collagen arthritis were treated daily, every other day or every third day with single subcutaneous (sc) injections of IL-1ra formulated in HA and the effects on arthritis determined. Results were compared to those obtained with IL-1ra in citrate buffered saline with EDTA and polysorbate (CSEP). Sequential blood levels were determined in rats injected sc with IL-1ra in CSEP or HA. RESULTS: Incorporation into HA led to slower release of IL-1ra into the bloodstream and maintained therapeutic blood levels of IL-1ra for a longer time compared to the IL-1ra/CSEP formulation. Single daily sc doses of 100 mg/kg IL-1ra in CSEP were ineffective in type II collagen arthritis. By contrast, once per day dosing of 100 mg/kg IL-1ra in HA provided 78% inhibition of paw swelling. Every other day dosing with 100 mg/kg IL-1ra in HA resulted in 62% inhibition. IL-1ra (100 mg/ kg in HA) given every third day provided 19% inhibition of arthritis. Improved efficacy correlated with improved pharmacokinetics. CONCLUSIONS: Administration of IL-1ra in the slow release vehicle HA improves pharmacokinetics and efficacy in rat type II collagen arthritis.     

Selenium and iodine deficiencies and selenoprotein function

The present study was designed to evaluate the roles of 5-HT2 and 5-HT3 receptors in the mouse forced swimming test, by using selective agonists and antagonists of 5-HT(2A/C) and 5-HT3 receptor sites. Agonists/antagonists and antidepressants were administered 45 min and 30 min, respectively, prior to testing. Pretreatment with (+/-)-2,5-dimethoxy-4-iodoamphetamine (DOI) (4 mg/kg, i.p.) or 2-methyl-5-HT (4 mg/kg, i.p.) had no effect on the anti-immobility effects of any antidepressant tested. Prior administration of ritanserin (4 mg/kg, i.p.) or ketanserin (8 mg/kg, i.p.), on the other hand, potentiated the effects of sub-active doses of imipramine (8 mg/kg, i.p.) and desipramine (16 mg/kg, i.p.) but not of maprotiline (8 mg/kg, i.p.), fluoxetine (16 mg/kg, i.p.), citalopram (16 mg/kg, i.p.) or fluvoxamine (8 mg/kg, i.p.). Pretreatment with ondansetron (1 X 10(-5) mg/kg, i.p.) enhanced the antidepressant-like effects of sub-active doses of the selective serotonin reuptake inhibitors. The results of the present study suggested that, in the forced swimming test, the selective serotonin reuptake inhibitors act partially through 5-HT3 receptor sites, whereas the tricyclic antidepressants exert effects at 5-HT(2A/C) receptor sites. Anti-immobility effects of the selective noradrenaline reuptake inhibitor, maprotiline, do not seem to be mediated by 5-HT(2A/C) or 5-HT3 receptor function.     

Opiates and medial hypothalamic knife cuts cause hyperphagia through different mechanisms.

In Exp I, male Sprague-Dawley rats were given bilateral parasagittal medial hypothalamic knife cuts (KCs) or a sham procedure and fed a high-fat diet. KC and sham-operated Ss were approximately equally sensitive to the suppressive effects of naloxone (0.1–20 mg/kg, subcutaneously [sc]) on food intake. Ketocyclazocine (0.1–20 mg/kg, sc) generally increased daytime food intake in sham-operated Ss; in contrast, the normal hyperphagia of KC Ss was in most cases either unchanged or decreased by ketocyclazocine. In Exp II, neither diet composition nor hypothalamic KCs significantly affected the feeding responses to naloxone or the stimulatory effects of butorphanol tartrate (0.1–20 mg/kg, sc). It was hypothesized that the differential effects of ketocyclazocine in KC and sham-operated Ss were a consequence of the sedative effects of the drug combined with the elevated baseline of the KC Ss. This hypothesis was supported by Exp III, which showed that ketocyclazocine also reduced nocturnal intake in unoperated Ss and that butorphanol increased intake. That feeding responses to naloxone and butorphanol were essentially unchanged by hypothalamic KCs suggests that the opioid feeding system is independent of the longitudinal feeding inhibitory pathway believed to be involved in KC-induced hyperphagia. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

HBED: the continuing development of a potential alternative to deferoxamine for iron-chelating therapy

To further examine the potential clinical usefulness of the hexadentate phenolic aminocarboxylate iron chelator N, N'-bis(2-hydroxybenzyl)ethylenediamine-N,N'-diacetic acid (HBED) for the chronic treatment of transfusional iron overload, we performed a subchronic toxicity study of the HBED monosodium salt in rodents and have evaluated the iron excretion in primates induced by HBED. The HBED-induced iron excretion was determined for the monohydrochloride dihydrate that was first dissolved in a 0.1-mmol/L sodium phosphate buffer at pH 7.6 and administered to the primates either orally (PO) at a dose of 324 micromol/kg (149.3 mg/kg, n = 5), subcutaneously (sc) at a dose of 81 micromol/kg (37.3 mg/kg, n = 5), sc at 324 micromol/kg (n = 5), and sc at 162 micromol/kg (74.7 mg/kg) for 2 consecutive days for a total dose of 324 micromol/kg (n = 3). In addition, the monosodium salt of HBED in saline was administered to the monkeys sc at a single dose of 150 micromol/kg (64.9 mg/kg, n = 5) or at a dose of 75 micromol/kg every other day for three doses, for a total dose of 225 micromol/kg (n = 4). For comparative purposes, we have also administered deferoxamine (DFO) PO and sc in aqueous solution at a dose of 300 micromol/kg (200 mg/kg). In the iron-loaded Cebus apella monkey, whereas the PO administration of DFO or HBED even at a dose of 300 to 324 micromol/kg was ineffective, the sc injection of HBED in buffer or its monosodium salt, 75 to 324 micromol/kg, produced a net iron excretion that was nearly three times that observed after similar doses of sc DFO. In patients with transfusional iron overload, sc injections of HBED may provide a much needed alternative to the use of prolonged parenteral infusions of DFO. Note: After the publication of our previous paper (Blood, 91:1446, 1998) and the completion of the studies described here, it was discovered that the HBED obtained from Strem Chemical Co (Newburyport, MA) that was labeled and sold as a dihydrochloride dihydrate was in fact the monohydrochloride dihydrate. Therefore, the actual administered doses were 81, 162, or 324 micromol/kg; not 75, 150, or 300 micromol/kg as was previously reported. The new data have been recalculated accordingly, and the data from our earlier study, corrected where applicable, are shown in parentheses.     

Effects of cycloheximide administered in conjunction with nicotine on retention of a passive avoidance task in mice.

Studied retention of a passive avoidance task in mice given either cycloheximide (30 mg/kg or 100 mg/kg sc) or cycloheximide in combination with nicotine (1.0 mg/kg, ip). Two similar experiments were conducted: In the 1st experiment, the effects of these drugs were studied in 45 inbred C57Bl/6J mice. In the 2nd experiment, the effects of these drugs were studied in 113 genetically heterogenous mice. Cycloheximide was found to have a deleterious effect on retention of the passive avoidance task. Larger doses of cycloheximide were found to be necessary to disrupt memory in heterogenous than C57Bl/6J Ss. Nicotine, when administered in conjunction with cycloheximide, abolished the memory disruptive effects of cycloheximide. Results are discussed in terms of a time-dependent consolidation model of memory storage. (36 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A vagally mediated histaminergic component of food-related drinking in the rat.

Six experiments with 95 male albino Sprague-Dawley rats (1) demonstrated that exogenous histamine was a potent stimulus for drinking behavior that was dependent upon an intact abdominal vagus and (2) provided evidence for a histaminergic component of the stimulus for food-related drinking in the rat. Histamine elicited drinking in a dose-related manner typically within 5 min after sc injection in Ss. Threshold for increased drinking was 1.25 mg/kg, and 2.5 mg/kg elicited half of the maximal drinking response that followed 20 mg/kg. Bilateral subdiaphragmatic vagotomy, with the hepatic branch left intact, severely attenuated drinking in response to systemic histamine: Vagotomized Ss drank later and less than did normal Ss after doses of histamine between 1.25 and 40 mg/kg. This attenuation was attributed to the destruction of vagal afferent fibers because histamine-elicited drinking was not affected by blockade of vagal efferents with atropine methyl nitrate. Drugs antagonistic to peripheral H? histamine receptors specifically inhibited drinking in response to histamine: Cimetidine or metiamide injected ip delayed and decreased drinking after sc histamine and temporarily decreased drinking after hypovolemia produced by sc polyethylene glycol, but failed to inhibit drinking after water deprivation, cellular dehydration, or isoproterenol. Finally, cimetidine or metiamide inhibited drinking in temporal association with a meal of liquid or solid food without slowing the rate of eating or decreasing food intake. (39 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strain comparisons of DFP neurotoxicity in rats

The purpose of this study was to assess intraspecies differences in behavioral and autonomic function in three strains of rat following administration of diisopropyl fluorophosphate (DFP), an irreversible inhibitor of acetylcholinesterase activity. Male rats of the Long-Evans (LE), Fischer 344 (F344), and Sprague-Dawley (SD) strains wer administered DFP at doses of 0-1.5 mg/kg (sc). The animals were placed 60 min later into one of two motor activity chambers and tested for 30 min. Motor activity was measured using either a Doppler-based system or a commercial photocell device. Following measurement of motor activity in the Doppler system, body temperature (Tb) was measured and blood was then withdrawn by cardiac puncture and analyzed for serum cholinesterase activity (ChE). The remaining rats were retested 1 d after DFP administration in the photocell device. The results showed a significant influence of strain on the effects of DFP. Motor activity of LE rats was reduced by DFP at doses of 1.0 and 1.5 mg/kg, whereas the activity of F344 rats was reduced only at 1.5 mg/kg. The relative sensitivity of SD rats depended on the device used to measure motor activity. The SD rats resembled F344 rats in their response to DFP when motor activity was measured in the photocell device, and LE rats when motor activity was measured in the Doppler system. The Tb of F344 rats was unaffected by DFP, while the LE and SD rats became hypothermic at 1.5 mg/kg. The DFP-induced inhibition of serum ChE activity was significantly less in F344 rats. All three strains retested the day after DFP still showed significant decreases in motor activity. Overall, it appears that the F344 strain is relatively resistant to the behavioral and autonomic effects of DFP. This intraspecies variability should be considered in selecting appropriate experimental models for assessing the neurotoxicological hazards of cholinesterase-inhibiting pesticides.