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  • 1
    ISSN: 1432-2072
    Keywords: Corticotropin-releasing factor ; Conflict test ; Chlordiazepoxide
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of corticotropin-releasing factor (CRF) in mediating the stress response was studied using a behavioral test in which anxiety or conflict influence performance. Rats implanted with intraventricular cannulae were tested in a Geller-Seifter conflict test modified for incremental shock. CRF produced a dose-dependent attenuation of punished and nonpunished responding in the conflict test. Chlordiazepoxide increased punished, but not unpunished, responding and produced a dose-dependent reversal of CRF-induced response suppression. CRF had no effect on tail flick or hot-plate analgesia tests. The results support the hypothesis that CRF produces behavioral effects consistent with “anxiety” or an increased responsiveness to stress.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Ethanol ; Withdrawal ; Anxiety ; Elevated plus-maze ; Corticotropin-releasing factor
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The role of the neuropeptide corticotropin-releasing factor (CRF) in mediating the behavioral effects of ethanol withdrawal in the rat was examined using the elevated plus-maze test. In Experiment 1, CRF (0.5 µg ICV) reduced the percentage of time spent on the open arms of the elevated plus-maze, consistent with an “anxiogenic-like” effect. CRF also reduced the total number of arm entries, indicating a reduction in general activity. Low doses (5 and 25 µg ICV) of the CRF antagonist, alpha-helical CRF produced no behavioral effects in the elevated plus-maze, while a higher dose (50 µg ICV) elicited CRF-like activity. In experiment 2, rats were maintained for 2–3 weeks on a liquid diet containing ethanol (8.5–11.5% v/v) or sucrose. Eight hours after withdrawal from the ethanol diet rats displayed “anxiogenic-like” responses as well as a reduction in general activity in the elevated plus-maze compared with rats withdrawn from control diet. Alpha-helical CRF significantly antagonized the “anxiogenic-like” effects of ethanol withdrawal in the plus-maze. General activity and physical signs of ethanol withdrawal such as tail stiffness, body tremor and ventromedial distal flexion were unaffected by alpha-helical CRF. Blood Alcohol Levels (BALs) determined immediately after removal of the ethanol diet showed no group differences in ethanol consumption. These results suggest that increased activity of central CRF systems may mediate the anxiogenic effects of ethanol withdrawal.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-2072
    Keywords: Key words Cocaine ; Chronic treatment ; Withdrawal ; Anxiety ; Defensive burying paradigm ; Elevated plus-maze ; Corticotropin-releasing factor ; Corticotropin-releasing factor antagonist ; D-Phe CRF(12 ; 41)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Rationale: Chronic cocaine abuse is associated with the development of anxiogenic states in humans. Corticotropin-releasing factor (CRF) is an endogenous neurotropic factor well known to modulate stress responses. It has been postulated that CRF is involved in the neurobiological mechanisms underlying the anxiety and/or stress responses associated with removal of cocaine after chronic administration. Objective: The present study investigated the role of endogenous CRF in mediating the “anxiety-like” effect 48 h after the cessation of saline or chronic cocaine treatment in rats, using the defensive burying paradigm and the elevated plus-maze. Methods: Rats received daily injections of cocaine (20 mg/kg IP, for 14 consecutive days) or vehicle. Forty-eight hours after the last injection, animals were tested in the plus-maze and then in the defensive burying paradigm. In a second experiment, intracerebroventricular (ICV) cannulae were implanted at the lateral ventricle. Animals were allowed a 1-week period for recovery before starting the chronic drug treatment. The defensive burying testing took place 48 h after cessation of the treatment. The CRF antagonist [DPhe12, Nle21,38, CαMe Leu37] r/h CRF(12–41), (also known as D-phe CRF(12–41)) (0.04, 0.2 and 1.0 μg/5 μl) was injected 5 min before the 15-min testing. Results: An “anxiogenic-like” effect following chronic cocaine treatment was demonstrated with the defensive burying paradigm, but not with the elevated plus-maze. This “anxiety-like” response was attenuated by ICV pretreatment with the CRF antagonist D-Phe CRF(12–41), with the highest dose of the CRF antagonist reversing the observed “anxiogenic-like” response. Conclusions: These data suggest that brain CRF may be substantially involved in the development of “anxiety-like” responses related to cocaine withdrawal and could be important for future drug dependence treatments.
    Type of Medium: Electronic Resource
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