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Subjective Effect of Monoamine Uptake Inhibitors in Rats Trained to Discriminate Citalopram
Author(s) -
Li LiBin,
Kopajtic Theresa A.,
Desai Rajeev I.,
Cyriac George C.,
Newman Amy H.,
Katz Jonathan L.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a779-b
Subject(s) - citalopram , sertraline , paroxetine , fluvoxamine , pharmacology , fluoxetine , reuptake inhibitor , antidepressant , serotonin , chemistry , monoamine neurotransmitter , psychology , medicine , receptor , hippocampus
Selective serotonin uptake inhibitors (SSRIs) are used in treatment of depression, and for other indications, however there are few studies of their interoceptive effects in animals. We examined effects of various monoamine uptake inhibitors in rats trained to discriminate the SSRI, (±)citalopram (10 mg/kg) from saline, and in displacement of [ 3 H]citalopram in rat midbrain membranes (nonspecific binding assessed with 10 μM fluoxetine). Rats were trained with food reinforcement to emit 1 response after citalopram and another after saline injection. Each 20 th response was reinforced, and saline or citalopram sessions occurred in a mixed sequence. Testing started when performance was >85% correct over 4 consecutive sessions). Dose‐dependent substitution for citalopram (ED 50 in μmol/kg) was obtained with alaproclate (14.6), citalopram (3.65), clomipramine (13.8), fluoxetine (7.26), fluvoxamine (4.17), LY 233,708 (0.53), paroxetine (3.29), and sertraline (10.1). In contrast, cocaine, WIN35,428 and nisoxetine failed to substitute across active doses. The affinities in displacement of [ 3 H]citalopram ranged from 0.25 to 43.8 nM, but were not significantly correlated with substitution potencies (r 2 =0.387, p=0.0995). Several SSRIs (alaproclate, fluoxetine, paroxetine, and sertraline), and cocaine, significantly decreased response rates with potencies unrelated to affinities (r 2 =0.0913, p=0.698). The results suggest that the citalopram discrimination is pharmacologically specific for serotonin uptake inhibition, and point to differences and similarities among SSRIs. Supported by IRP/NIDA/NIH.