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  • 1995-1999  (3)
  • Firing  (2)
  • CCK-A and CCK-B receptor antagonists  (1)
  • 1
    ISSN: 1432-1912
    Keywords: Fluoxetine ; Paroxetine ; Serotonin ; 5-HT1A autoreceptors ; Dorsal raphe nucleus ; Firing ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Electrophysiological and autoradiographic approaches were used to assess possible changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat dorsal raphe nucleus after a subchronic treatment with fluoxetine or paroxetine, two specific serotonin reuptake inhibitors with antidepressant properties. Fluoxetine or paroxetine were injected daily (5 mg/kg, i.p.) for various time periods up to 21 days. Electrophysiological recordings performed 24 h after the last injection showed that the potency of the 5HT1A receptor agonist, 8-OH-DPAT, to depress the firing of serotoninergic neurons in the dorsal raphe nucleus within brain stem slices was significantly reduced as early as after a 3-day treatment with either drug. The proportion of recorded neurons showing desensitization of somatodendritic 5-HT1A autoreceptors increased along the treatment from ∼40% on the 3rd day to 60–80% on the 21st day. At no time during the treatment, was the specific binding of [3H]8-OHDPAT (agonist radioligand) or [3H] WAY-100 635 (antagonist radioligand) to 5-HT1A receptors modified in the dorsal raphe nucleus or in other brain areas, suggesting that neither the density nor the coupling of these receptors to G-proteins were probably altered in rats injected with fluoxetine or paroxetine for up to 21 days. These results show that adaptive desensitization of somatodendritic 5-HT1A autoreceptors within the dorsal raphe nucleus can already be detected after a 3-day treatment with selective serotonin reuptake inhibitors. Rather than the desensitization per se, it may be the progressive increase in the number of serotoninergic neurons with desensitized 5-HT1A autoreceptors which plays a critical role in the (slowly developing) antidepressant action of these drugs.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1912
    Keywords: Key words Fluoxetine ; Paroxetine ; Serotonin ; 5-HT1A autoreceptors ; Dorsal raphe nucleus ; Firing ; Autoradiography
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Electrophysiological and autoradiographic approaches were used to assess possible changes in 5-hydroxytryptamine (serotonin) 5-HT1A receptors in the rat dorsal raphe nucleus after a subchronic treatment with fluoxetine or paroxetine, two specific serotonin reuptake inhibitors with antidepressant properties. Fluoxetine or paroxetine were injected daily (5 mg/kg, i.p.) for various time periods up to 21 days. Electrophysiological recordings performed 24 h after the last injection showed that the potency of the 5-HT1A receptor agonist, 8-OH-DPAT, to depress the firing of serotoninergic neurons in the dorsal raphe nucleus within brain stem slices was significantly reduced as early as after a 3-day treatment with either drug. The proportion of recorded neurons showing desensitization of somatodendritic 5-HT1A autoreceptors increased along the treatment from ∼40% on the 3rd day to 60–80% on the 21st day. At no time during the treatment, was the specific binding of [3H]8-OH-DPAT (agonist radioligand) or [3H]WAY-100 635 (antagonist radioligand) to 5-HT1A receptors modified in the dorsal raphe nucleus or in other brain areas, suggesting that neither the density nor the coupling of these receptors to G-proteins were probably altered in rats injected with fluoxetine or paroxetine for up to 21 days. These results show that adaptive desensitization of somatodendritic 5-HT1A autoreceptors within the dorsal raphe nucleus can already be detected after a 3-day treatment with selective serotonin reuptake inhibitors. Rather than the desensitization per se, it may be the progressive increase in the number of serotoninergic neurons with desensitized 5-HT1A autoreceptors which plays a critical role in the (slowly developing) antidepressant action of these drugs.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
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  • 3
    ISSN: 1432-2072
    Keywords: Anxiety ; Cholecystokinin ; CCK-A and CCK-B receptor antagonists ; CCK-B receptor agonists ; Behavioural suppression ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of cholecystokinin (CCK) receptor ligands were studied in the rat safety signal withdrawal conflict procedure, an operant paradigm sensitive to both anxiolytic and anxiogenic compounds. In this procedure, behavioural suppression of lever pressing for food was induced by the withdrawal of a conditioned signal for safety without the usual presentation of a conditioned signal for danger. The compounds tested were selective CCK-B antagonists [CI-988 (0.01–1 mg/kg SC), L-365,260 (0.004–2 mg/kg IP) and LY 262,691 (0.001–1 mg/kg SC)], CCK-B agonists [CCK-4 (0.01–1 mg/kg SC) and BC 264 (0.004–1 mg/kg IP)] and CCK-A antagonists [devazepide (0.001–1 mg/kg SC) and lorglumide (0.01–1 mg/kg SC)]. None of these drugs induced the expected behavioural effects, i.e. an anxiolytic-like release of the behavioural suppression with CCK-B and, possibly, CCK-A antagonists and/or a further reduction of lever pressing with CCK-B agonists, indicative of an anxiogenic-like potential. In contrast, the established anxiolytic lorazepam (0.06–0.25 mg/kg IP), as well as diazepam (2 mg/kg IP) and buspirone (0.25 mg/kg SC) used as positive control drugs, released the suppression of pressing for food during the period associated with the safety signal withdrawal, whereas picrotoxin (1 mg/kg IP), used as an anxiogenic control, further reduced responding during this conflict period. The present results contrast with a series of published data suggesting the involvement of CCK processes in anxiety-related behaviour in rodent models such as the elevated plus-maze or the light:dark two compartment test, and in panic disorders in humans. They indicate that the behavioural effects of one category of drugs might vary considerably, depending on the experimental situation. Furthermore, they allow the conclusion that anticipatory anxiety generated by withdrawal of conditioned signals for safety does not involve CCK-related processes.
    Type of Medium: Electronic Resource
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