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  • 1
    ISSN: 1471-4159
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Abstract: Male, Fischer strain 344 adult rats were given various doses (25–100 mg/kg) of p,p′-DDT by oral gavage, and levels of biogenic amines, their metabolites, and amino acid neurotransmitters, tremor activity, and rectal temperature were measured at several intervals (2, 5, 12, and 24 h) after dosing. Dose-related increases in rectal temperature and in tremor activity were observed at 50–100 mg/kg 12 h after dosing. Tremorigenic doses of DDT increased the 5-hydroxyindoleacetic acid (5-HIAA) level in hypothalamus, brainstem, and striatum, whereas doses of 75 and 100 mg/kg increased the 3-methoxy-4-hydroxyphenylglycol (MHPG) level in hypothalamus and brainstem and the 3,4-dihydroxyphenylacetic acid level in striatum. Six amino acids were assayed in the brainstem, hypothalamus, and striatum; aspartate and glutamate levels were increased only in brainstem at 25–100 mg/kg. No consistent changes in concentrations of taurine, glutamine, glycine, or γ-aminobutyric acid were observed in any of the regions assayed. Time-related increases in rectal temperature were seen 2–12 h after dosing, and the presence of tremor was observed 5–12 h after dosing; for both the time of peak effect was at 12 h. The DDT-induced hyperthermia and tremor were associated with dose- and time-related increases in levels of 5-HIAA, MHPG, aspartate, and glutamate. It is suggested that an increase in the turnover rate of 5-hydroxy-tryptamine (5-HT) may be responsible for the DDT-induced hyperthermia, whereas increases in the metabolism of 5-HT and norepinephrine may be involved in the tremor.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Pharmacology 24 (1984), S. 425-450 
    ISSN: 0362-1642
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 86 (1985), S. 426-431 
    ISSN: 1432-2072
    Keywords: DDT ; Tremor ; Trihexyphenidyl ; 5,5-Diphenylhydantoin ; Pizotifen ; Mephenesin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rats given a tremorigenic dose of DDT (75 mg/kg, PO) were treated with pharmacological agents either 30 min prior to DDT or 1–2 h prior to testing at the time of peak effect (12 h postdosing). The administration of mephenesin (a centrally acting muscle relaxant) or Dilantin (an anticonvulsant) prior to DDT significantly attenuated tremor. Pretreatment with pizotifen (a serotonergic receptor antagonist) had no significant effect on tremor. Administration of the same agents 1–2 h prior to measurement had minimal effects. Trihexyphenidyl (a muscarinic cholinergic receptor antagonist) exacerbated the tremor produced by DDT. These data suggest that cholinergic neurotransmitter systems may be involved in DDT-induced tremor. That DDT-induced tremor was significantly attenuated by mephenesin and Dilantin is in accord with the conclusion that DDT-induced tremor is a manifestation of repetitive discharge due to interference with ionic conductance.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 92 (1987), S. 398-401 
    ISSN: 1432-2072
    Keywords: Baclofen ; Memory ; Passive avoidance ; GABA receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Baclofen (Lioresal, Ciba-Geigy) is an analog of the inhibitory neurotransmitter GABA and is used clinically to control spasticity. Recent studies have demonstrated that this compound produces a marked inhibition of synaptically evoked responses in area CA3 of the hippocampal slice, suggesting that this drug could influence behavior mediated by the limbic system. In the present study, male rats of the Fischer-344 strain were trained on a one-trial passive avoidance task and tested for retention 1 week later. After the training trial, separate groups of rats received either 5 or 10 mg/kg/4 ml IP of baclofen or the distilled H2O vehicle immediately, 10 min, or 60 min after training. One week later, the rats that received baclofen immediately after training reentered the test chamber with a significantly higher frequency than controls, although no differences in vacillatory responses were observed between groups. Similar effects were observed following posttrial administration of chlordiazepoxide. In a separate experiment rats were tested for locomotor activity after receiving the same doses of baclofen. Although baclofen decreased activity during a 30-min period after dosing, rats exposed to baclofen showed no significant change in activity relative to controls 1 week later. These data are consistent with the interpretation that baclofen may interfere with memory consolidation or retention.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 91 (1987), S. 320-325 
    ISSN: 1432-2072
    Keywords: Tremor ; Acoustic startle ; Chlordecone ; DDT ; Adrenergic system ; Calcium
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Pretreatment of rats with phenoxybenzamine (5 mg/kg; SC), an alpha adrenergic antagonist, decreased the peak tremor power and startle magnitude of rats subsequently given DDT (75 mg/kg; PO) or chlordecone (60 mg/kg; IP), without having a significant effect on control animals. Pretreatment with an intracerebroventricular injection of calcium (3.75 μM in 5 μl NaCl) decreased the peak tremor power due to subsequently administered DDT, while increasing the tremor response in rats later dosed with chlordecone. The effects of phenoxybenzamine are postulated to be due to a blockade of an excitatory influence of the adrenergic system. Calcium may decrease DDT-induced tremor by acting as a neuronal stabilizer. Potentiation of the tremorigenic effect of chlordecone by calcium may be due to increased levels of intracellular calcium, resulting in augmented release of neurotransmitters in chlordecone-exposed animals.
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  • 6
    ISSN: 1432-2072
    Keywords: R-DOM ; S-Amphetamine ; State-dependent discriminative responding ; Generalization of drug-induced stimuli
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of 0.75 mg/kg of R-DOM and 1.0 mg/kg of S-amphetamine served as discriminative stimuli in the control of a two-lever discrimination response. Dose-response evaluation of the two agents indicated that in S-amphetamine-trained animals the drug effects produced by test doses of 0.5 to 2.2 mg/kg of S-amphetamine could be considered as a dose-dependent continuum of low to high stimulus intensity. In R-DOM trained subjects, low to moderate doses of R-DOM (0.5–1.5 mg/kg) produced dose-related discriminative responding, but the high dose of R-DOM (2.2 mg/kg) resulted in random responding. When animals trained to discriminate 1.0 mg/kg of S-amphetamine from saline were given 0.5 or 0.75 mg/kg of R-DOM, they tended to respond on the drug correct lever. However, higher doses of R-DOM (1.5 and 2.2 mg/kg) produced random responding. Similarly, animals trained to discriminate 0.75 mg/kg of R-DOM from saline exhibited correct responses following 0.5 and 0.75 mg/kg of S-amphetamine, but not after 1.5 and 2.2 mg/kg. These data suggest that low doses of R-DOM produce discriminative stimuli that are qualitatively different from those of higher doses. Stimuli following low doses of R-DOM also appear similar in some respects to those following low doses of S-amphetamine.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-2072
    Keywords: DOM and amphetamine comparisons ; Operant behavior ; Motor activity ; Brain catecholamines ; Brain serotonin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A comparison of the behavioral pharmacology of DOM and amphetamine in rats indicated that lower doses (0.10–1.0 mg/kg) of the two agents had similar effects on schedule-controlled food-reinforced and shock-avoidance behavior. Similarities were also noted in their effects on horizontally directed motor activity when testing was preceded by a period of acclimation. However, most doses of DOM tended to decrease unacclimated motor activity, while amphetamine increased this behavior. Neuropharmacological antagonism studies indicated that brain catecholamines (CA) and serotonin (5-HT) are involved in the behavioral effects of both DOM and amphetamine. Cinanserin, a 5-HT receptor blocker, attenuated the behavioral disruptive effects of both agents on food-reinforced responding. Cinanserin attenuated the effects of all doses of DOM and those of higher doses of amphetamine on shock avoidance. When given prior to lower doses of amphetamine, there was a greater behavioral stimulation than when amphetamine was given alone. Prior depletion of brain CA with α-methyltyrosine (α-MT) did not affect DOM induced disruption of food-reinforced responding, while α-MT attenuated the behavioral effects of all doses of DOM and amphetamine on shock avoidance. These data suggest that DOM and amphetamine share a similar component in their mechanism of action which depends on the availability of a releasable pool of brain CA.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 19 (1971), S. 313-323 
    ISSN: 1432-2072
    Keywords: Mescaline ; Operant Behavior ; Tolerance ; Intraventricular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A fixed-ratio schedule of food reinforcement (FR 30) was used to study the differences in tolerance produced by peripheral injections and intraventricular infusions of mescaline hydrochloride in rats. Successive daily administrations of 10 mg mescaline/kg i.p. resulted in a decrease in behavioral disruption (tolerance). The following day, intraventricular infusion of a dose of mescaline previously shown to be approximately equal to the peripheral dose in terms of behavioral disruption was started. After tolerance to central administration of mescaline was established, 10 mg/kg of mescaline injected i.p. resulted in behavioral disruption equal to that produced by the first i.p. injection. In a second experiment, blood pressure effects of mescaline given i.p. and intraventricularly were studied. Peripherally administered mescaline produced marked effects on caudally measured blood pressure and increased biting upon and struggling within the restraining device. Mescaline administered centrally did not appear to elicit similar cardiovascular changes. These data suggest that different mechanisms may be involved in the formation of tolerance to mescaline administered by these two routes as measured by means of a fixed ratio reinforcement schedule.
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  • 9
    ISSN: 1432-0738
    Keywords: Key words Polychlorinated biphenyls ; Calcium sequestration ; Cerebellum ; 45Ca2+-uptake ; In vitro ; Structure-activity relationships
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Recent studies from our laboratory indicate that polychlorinated biphenyl (PCB) congeners in vitro perturbed signal transduction mechanisms including cellular Ca2+-homeostasis and protein kinase C translocation. We have now investigated the structure-activity relationship (SAR) of three PCB mixtures, 24 PCB congeners and one dibenzofuran for their effects on microsomal and mitochondrial Ca2+-sequestration in rat cerebellum. Ca2+-sequestration by these intracellular organelles was determined using radioactive 45CaCl2. All three mixtures studied, Aroclor 1016, Aroclor 1254 and Aroclor 1260, were equally potent in inhibiting microsomal and mitochondrial Ca2+-sequestration with IC50 values of 6–8 μM. 1,2,3,7,8-Pentachlorodibenzofuran had no effect on Ca2+-sequestration by these organelles. The SAR among the congeners revealed: (1) congeners with ortho-/meta- or ortho-, para-chlorine substitutions were the most potent in inhibiting microsomal and mitochondrial Ca2+-sequestration (IC50=2.4–22.3 μM); (2) congeners with only para- but without ortho-substitutions were not effective in inhibiting Ca2+-sequestration by microsomes and mitochondria; (3) increased chlorination was not related to the effectiveness of these congeners. The present SAR studies indicate that the effects of most PCB congeners in vitro may be related to an interaction at specific sites having preference for low lateral substitution or lateral content (meta- or para) in the presence of ortho-substitution.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Psychopharmacology 23 (1972), S. 220-230 
    ISSN: 1432-2072
    Keywords: Mescaline ; d-Amphetamine ; Tolerance ; Cross-Tolerance ; Intraventricular
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Differences in tolerance and cross-tolerance to the behavioral effects of d-amphetamine sulfate and mescaline hydrochloride were studied as a function of intraventricular or intraperitoneal routes of administration. Operant behavior, using a fixed ratio schedule of food reinforcement, was the behavioral variable. Following tolerance to d-amphetamine infused intraventricularly, an approximately equipotent dose of mescaline, similarly administered the next day, resulted in behavioral disruption indicating a lack of cross-tolerance. However, following tolerance to mescaline administered intraventricularly, an equipotent dose of d-amphetamine infused the next day did not result in behavioral disruption, indicating cross-tolerance, When d-amphetamine (1.6 or 2.5 mg/kg) and mescaline (10 mg/kg) were administered peripherally (i.p.), no cross-tolerance was found, regardless of the order of drug presentation. Finally, tolerance to amphetamine administered intraventricularly was not indicative of tolerance to amphetamine given intraperitoneally. The next day (after central tolerance) amphetamine disrupted the operant to an equal or greater extent than it had prior to central tolerance formation. This is further evidence that drugs administered directly into the CNS may not be producing their behavioral effects in the same manner as they do via peripheral administration.
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