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  • 1
    Electronic Resource
    Electronic Resource
    Low doses of corticotropin-releasing factor potentiate amphetamine-induced stereotyped behavior (1989)
    Springer
    Psychopharmacology 99 (1989), S. 27-33 
    Details
    ISSN: 1432-2072
    Keywords: Corticotropin-releasing factor (CRF) ; Amphetamine ; Stereotypy ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that is critically involved in the activation of the hypothalamic-pituitary adrenal axis during stress. In addition, it has been suggested that extrahypothalamic CRF may be important in initiating behavioral responses to stressful events. In the present experiment, we examined the effects of central administration of CRF on amphetamine-induced stereotyped behavior. Amphetamine-induced stereotyped behavior has been considered as a behavioral strategy to cope with excessive arousal. Low doses of CRF (0.02 and 0.1 μg), administered into the lateral ventricle (ICV), were shown to potentiate amphetamine (4.0 mg/kg; SC)-induced stereotyped behavior, as measured by the Creese and Iversen rating scale and behavioral observations. These low doses of CRF specifically enhanced the tendency for rats to sniff with their heads down 20 min after injection, and induced licking behavior later during testing. In contrast, the rats treated with a higher dose of CRF (0.5 μg, ICV) showed more locomotor activity throughout the test, but did not differ from the saline-treated animals in the intensity of amphetamine-induced stereotyped behavior.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00634448
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  • 2
    Electronic Resource
    Electronic Resource
    Effects of benzodiazepine receptor ligands on the performance of an operant delayed matching to position task in rats: opposite effects of FG 7142 and lorazepam (1994)
    Springer
    Psychopharmacology 115 (1994), S. 350-357 
    Details
    ISSN: 1432-2072
    Keywords: Delayed matching to position ; Short term memory ; Benzodiazepine receptor ; β-Carboline ; Inverse agonist ; FG 7142 ; Lorazepam ; Ro 15-4513
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of a series of benzodiazepine (BZ) receptor ligands, ranging from a full agonist through to partial inverse agonists, were examined on short term working memory in the rat. The behavioural paradigm used was a discrete trial, operant delayed matching to position task, as originally described by Dunnett (1985), with delays of 0, 5, 15 and 30 s. The benzodiazepine receptor (BZR) full agonist lorazepam (0.25, 0.375 and 0.5 mg/kg) dose and delay dependently impaired matching accuracy. Lorazepam also increased the latency to respond and decreased the number of nose pokes made into the food tray during the delays. In contrast, the BZR partial agonist ZK 95 962 (1, 3, 10 mg/kg) did not affect matching accuracy, but did increase the speed of responding. The BZR antagonist ZK 93 426 (1.25, 5, 25 mg/kg) had no effects in this paradigm. The BZR weak partial inverse agonists Ro 15-4513 (0.1, 1 and 10 mg/kg) and ZK 90 886 (1, 3 and 10 mg/kg) did not affect accuracy of performance. However, both of these drugs increased the latency to respond and decreased nose poke responses. These motoric effects were particularly strong following 10 mg/kg Ro 15-4513. This shows that the effects of drugs on the accuracy of responding and on the speed of responding can be dissociated. The BZR partial inverse agonist FG 7142 had effects on matching accuracy that were dependent upon dose. The lowest dose of FG 7142 (1 mg/kg) significantly improved accuracy, whereas the highest dose (10 mg/kg) impaired accuracy. This impairment induced by FG 7142 (10 mg/kg) was accompanied by an increase in the latency to respond and a decrease in the number of nose pokes. Taken together, these results show that the accuracy of delayed matching performance can be modulated in opposite ways by the BZR full agonist lorazepam and a low dose of the BZR partial inverse agonist, FG 7142.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245076
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  • 3
    Electronic Resource
    Electronic Resource
    Effects of benzodiazepine receptor partial inverse agonists in the elevated plus maze test of anxiety in the rat (1995)
    Springer
    Psychopharmacology 121 (1995), S. 118-126 
    Details
    ISSN: 1432-2072
    Keywords: Anxiety ; Plus maze ; Rat ; Benzodiazepine receptor ; DMCM ; FG 7142 ; Yohimbine ; Pentylenetetrazol ; β-Carboline ; Inverse agonist
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The present series of experiments examined the effects of five benzodiazepine receptor (BZR) partial inverse agonists on the behaviour of rats on an elevated plus maze. The drugs were tested in a standard plus maze with 3-cm walls added to the open arms, as this has been shown to increase the sensitivity of the plus maze to anxiogenic-like drug effects (Jones and Cole 1995). The drugs tested were FG 7142 (0–100 mg/kg),β-CCE (0–30 mg/kg), ZK 132 556 (0–100 mg/kg), ZK 90 886 (0–30 mg/kg) and Ro 15–4513 (0–30 mg/kg). In addition, to allow a comparison with previous studies, the effects of three reference substances, DMCM (0–2.5 mg/kg), pentylenetetrazol (PTZ; 0–30 mg/kg) and yohimbine (0–5 mg/kg), were also examined. These three reference compounds produced a dose-dependent reduction in the duration of open arm exploration and the total number of open arm entries, indicative of anxiogenic-like effects. DMCM produced significant effects at the doses of 1.25 and 2.5 mg/kg, PTZ at 30 mg/kg, and yohimbine at 5 mg/kg. The BZR partial inverse agonist FG 7142 (10, 30 and 100 mg/kg) also reduced the duration of open arm exploration and the total number of arm entries. The minimally effective dose resulted in a receptor occupancy of approximately 80%. Ro 15–4513 also produced anxiogenic-like effects, but only at a dose (30 mg/kg) that resulted in a receptor occupancy of approximately 95%. In contrast, the other BZR partial inverse agonists, ZK 132 553 and ZK 90 886, did not significantly reduce the duration of open arm exploration, even at doses that produced greater than 95% receptor occupancies.β-CCE also did not reduce open arm exploration at any dose tested (0–30 mg/kg). The GABA shift, a biochemical index of intrinsic activity, indicates that these latter three compounds are more inverse agonistic than Ro 15–4513. In summary, these results demonstrate that not all BZR receptor partial inverse agonists have anxiogenic-like activity in the rat plus maze, and that the GABA shift, a biochemical index of intrinsic efficacy, does not predict which BZR partial inverse agonists are anxiogenic.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245598
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  • 4
    Electronic Resource
    Electronic Resource
    Comparison of several benzodiazepine receptor ligands in two models of anxiolytic activity in the mouse: an analysis based on fractional receptor occupancies (1994)
    Springer
    Psychopharmacology 114 (1994), S. 191-199 
    Details
    ISSN: 1432-2072
    Keywords: Abecarnil ; Alpidem ; Alprazolam ; Bretazenil ; Diazepam ; ZK 95962 ; β-Carboline ; Anxiolytics ; Receptor occupancy ; Four-plate test ; Plus-maze ; Mouse
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract This study compared the effects of the β-carboline anxiolytic, abecarnil, with other benzodiazepine receptor (BZR) ligands, including the full agonists diazepam and alprazolam, and the partial agonists ZK 95962 and bretazenil (Ro 16-6028), and alpidem, in the mouse four-plate test and plus-maze. The efficacy and potency of each compound was related to the fraction of BZR occupied by the drug. Abecarnil was efficacious in both tests and showed anxiolytic effects comparable with alprazolam and diazepam. In the four-plate test, abecarnil, bretazenil, and ZK 95962 had selective effects on releasing exploratory locomotor activity suppressed by footshock (punished crossings). None of these compounds significantly altered non-punished crossings. In contrast, diazepam and alprazolam increased both unpunished and punished crossings at low to medium doses (receptor occupancies of approximately 20–60%). The number of punished and unpunished crossings fell to control levels or below at higher, more sedative doses (approximately 80% receptor occupancy). Alpidem had very weak anxiolytic-like effects in this test and markedly reduced unpunished crossings at relatively low receptor occupancies (〉 15%). In the plus-maze, abecarnil increased the time spent in the open arms and the percentage open arm entries to an extent equal to that observed following diazepam or alprazolam administration. Bretazenil and ZK 95962 had weak effects on the measures of anxiolytic activity in this test. Alpidem also had little anxiolytic-like activity in the plus-maze but markedly reduced the total number of arm entries. The fractional BZR occupancies required to increase the time spent in the open arms of the maze to 250% of control levels were approximately 45% for abecarnil and alprazolam, 60% for diazepam, and 100% for ZK 95962. Bretazenil did not reach this potentiation at the doses tested (up to 89% receptor occupancy). Abecarnil appeared to act as a full agonist on the measures of anxiolytic activity in both tests (i.e. required low fractional BZR occupancies) but on the measures of stimulation or sedation was more similar to the BZR partial agonists (i.e. had no significant effects even at receptor occupancies approaching 100%). On this basis abecarnil could be described as a “selective agonist”. In general, the four-plate test was more sensitive than the plus-maze. For example, lower BZR occupancies were needed to produce significant anxiolytic effects in the four-plate test than in the plus-maze. In addition, the partial agonists bretazenil and ZK 95962, which both produced weak effects in the plus-maze, had similar anxiolytic potencies to the full BZR agonists, diazepam and alprazolam, in the four-plate test.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02244836
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  • 5
    Electronic Resource
    Electronic Resource
    Double dissociation between the effects of muscarinic antagonists and benzodiazepine receptor agonists on the acquisition and retention of passive avoidance (1995)
    Springer
    Psychopharmacology 118 (1995), S. 37-41 
    Details
    ISSN: 1432-2072
    Keywords: Passive avoidance ; Learning ; Memory Scopolamine ; Atropine ; Diazepam ; Lorazepam Rats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Both muscarinic antagonists, such as scopolamine, and benzodiazepine receptor (BZR) agonists, such as diazepam, produce a reliable impairment in the performance of one trial passive avoidance. Such deficits are frequently interpreted as drug-induced amnesia. However, these deficits could also result from a learning impairment. The present experiments compared the effects of two BZR agonists, lorazepam (0, 0.125, 0.25, and 0.375 mg/kg, IP) and diazepam (0, 0.78, 1.56, and 3.13 mg/kg, IP) with the effects of two muscarinic antagonists, scopolamine (0, 0.6, 0.8 and 1.0 mg/kg, SC) and atropine (0, 15, 30 and 60 mg/kg, IP) on a multiple trial passive avoidance task. In this procedure, the rats were trained with a 5-min inter-trial interval until a learning criterion was achieved. Retention was assessed 24 h later. This enabled the effects of the drugs on the acquisition and the retention of a passive avoidance response to be dissociated. Both atropine and scopolamine produced a marked impairment in the acquisition of the passive avoidance response, but did not impair retention. In contrast, diazepam and lorazepam did not alter the acquisition of a passive avoidance response, but did produce a dose-dependent impairment of retention. These results therefore demonstrate a double dissociation between the effects of muscarinic antagonists and BZR agonists on the acquisition and retention of passive avoidance.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245247
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  • 6
    Electronic Resource
    Electronic Resource
    5-HT1A receptor agonists improve the performance of normal and scopolamine-impaired rats in an operant delayed matching to position task (1994)
    Springer
    Psychopharmacology 116 (1994), S. 135-142 
    Details
    ISSN: 1432-2072
    Keywords: Short term memory ; Delayed matching to position ; 5-HT ; 5-HT1A receptor ; 8-OH DPAT ; Ipsapirone ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A series of experiments examined the effects of 5-HT1A ligands alone and in combination with the muscarinic antagonist scopolamine on short term working memory in the rat. The behavioural paradigm was a discrete trial, operant delayed matching to position task, with delays of 0, 5, 15 and 30 s. The 5-HT1A ligands tested were the full agonist, 8-OH DPAT (0, 0.1, 0.3 and 1 mg/kg), the partial agonist, ipsapirone (0, 1, 3 and 10 mg/kg), and the purported antagonist, NAN 190 (0, 1, 2, and 4 mg/kg). 1-PP (0, 0.1, 0.3, 1 mg/kg), the major metabolite of ipsapirone, was also tested. The lowest dose of 8-OH DPAT significantly improved matching accuracy at the longest delay, whereas the highest dose impaired matching accuracy and increased the latency to respond. Ipsapirone also significantly improved the accuracy of performance at a dose of 3 mg/kg, but the doses of 1 and 10 mg/kg did not significantly affect performance. NAN-190, at the highest dose tested (4 mg/kg), impaired matching accuracy, whereas the two lower doses did not significantly affect performance. The highest dose also increased the latency to respond. 1-PP had no effect on performance. Scopolamine HBr (0.14 mg/kg) caused a delay dependent impairment in matching accuracy, and had no effect on missed trials or the latency to respond. Low doses of 8-OH DPAT (0.1 and 0.3 mg/kg) significantly attenuated the scopolamine induced accuracy impairment, whereas 1 mg/kg 8-OH DPAT potentiated the impairment. Ipsapirone (3 mg/kg) also significantly improved the performance of scopolamine impaired rats. NAN-190 increased the latency to respond and reduced the number of nose pokes made during the delays in scopolamine-treated rats, and tended to potentiate the scopolamine-induced accuracy impairment. 1-PP did not affect the performance of scopolamine treated rats. Taken together, these results suggest that modulation of 5-HT1A receptors influences short term spatial working memory in the rat.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF02245055
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