Journal of psychopharmacology
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J. Psychopharmacol. (Oxford) · Apr 2012
D1 and D2 dopaminergic systems in the rat basolateral amygdala are involved in anxiogenic-like effects induced by histamine.
Involvement of the dopamine receptors in the basolateral amygdala (BLA) in the effects of histamine on anxiety-like behaviors of the elevated plus maze in male Wistar rats was investigated. The results showed that bilateral intra-BLA injections of histamine (2.5, 5 and 7.5 µg/rat) induced an anxiogenic-like effect, revealed by decreases in percentage of open arm time (%OAT) and open arm entries (%OAE). Intra-BLA administration of dopamine D1 receptor agonist, SKF38393 (0.25 µg/rat), and dopamine D2 receptor agonist, quinpirole (0.03 and 0.05 µg/rat), decreased %OAT but not %OAE. ⋯ On the other hand, intra-BLA pretreatment with a silent dose of SCH23390 (0.25 µg/rat) or sulpiride (0.1 µg/rat) prevented the anxiogenic-like effect of higher doses of histamine (5 and 7.5 µg/rat). No significant change was observed in total closed arm entries, as an index for motor activity of the animals. It can be concluded that the dopamine D1 and D2 receptors in the BLA may be involved in the anxiogenic-like effects induced by histamine.
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J. Psychopharmacol. (Oxford) · Apr 2012
Randomized Controlled TrialSwitching from long-term benzodiazepine therapy to pregabalin in patients with generalized anxiety disorder: a double-blind, placebo-controlled trial.
To evaluate the efficacy of pregabalin in facilitating taper off chronic benzodiazepines, outpatients (N = 106) with a lifetime diagnosis of generalized anxiety disorder (current diagnosis could be subthreshold) who had been treated with a benzodiazepine for 8-52 weeks were stabilized for 2-4 weeks on alprazolam in the range of 1-4 mg/day. Patients were then randomized to 12 weeks of double-blind treatment with either pregabalin 300-600 mg/day or placebo while undergoing a gradual benzodiazepine taper at a rate of 25% per week, followed by a 6-week benzodiazepine-free phase during which they continued double-blind study treatment. Outcome measures included ability to remain benzodiazepine-free (primary) as well as changes in Hamilton Anxiety Rating Scale (HAM)-A and Physician Withdrawal Checklist (PWC). ⋯ Treatment with pregabalin was associated with significantly greater endpoint reduction in the HAM-A total score versus placebo (-2.5 vs +1.3; p < 0.001), and lower endpoint mean PWC scores (6.5 vs 10.3; p = 0.012). Thirty patients (53%) in the pregabalin group and 19 patients (37%) in the placebo group completed the study, reducing the power to detect a significant difference on the primary outcome. The results on the anxiety and withdrawal severity measures suggest that switching to pregabalin may be a safe and effective method for discontinuing long-term benzodiazepine therapy.