title: Subacute fluoxetine enhances conditioned responding and conditioning-specific reflex modification of the rabbit nictitating membrane response:  implications for drug treatment with selective serotonin reuptake inhibitors.
abstract: Extensive research on the rabbit nictitating membrane response (NMR) has shown that the NMR reflex can become exaggerated following classical fear conditioning. This learning-related change is referred to as conditioning-specific reflex modification (CRM) and is observed in the absence of the conditioned stimulus. The aim of the current study was to examine the sensitivity of the CRM paradigm to serotonergic manipulation with fluoxetine, a commonly prescribed selective serotonin reuptake inhibitor for anxiety disorders. To assess the effect of fluoxetine on exaggerated reflexive responding indicative of CRM and on conditioned cued fear, rabbits underwent delay NMR conditioning (pairings of tone and periorbital shock) and were tested for CRM, followed by 5 days of daily fluoxetine (0.03, 0.3, or 3.0 mg/kg) or saline injections. CRM was reassessed 1 day and 1 week later, followed by a retention test of conditioned responses (CRs) to the tone. Fluoxetine (3.0 mg/kg) enhanced CRM and retention of conditioned responses, a week after treatment ceased, and this is in agreement with the reports on increased anxiety-like behaviors in other animal models and humans. The CRM paradigm, therefore, may provide important insight into the mechanisms underlying the paradoxical selective serotonin reuptake inhibitor effects.
authors.affiliation: Department of Physiology and Pharmacology, Blanchette Rockefeller Neurosciences Institute, West Virginia University, Morgantown, West Virginia 26506, USA. lburhans@brni.org
authors.forename: Lauren B
authors.initials: LB
authors.lastname: Burhans
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Smith-Bell
authors.forename: Bernard G
authors.initials: BG
authors.lastname: Schreurs
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001007:Anxiety / Q000139:chemically induced; D003214:Conditioning, Classical / Q000187:drug effects; D003215:Conditioning, Eyelid / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005239:Fear / Q000187:drug effects; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D009541:Nictitating Membrane / Q000187:drug effects*; D011817:Rabbits; D011897:Random Allocation; D012018:Reflex / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects*; D059326:Serotonergic Neurons / Q000187:drug effects*; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D059551:Toxicity Tests, Subacute
chemical_list: D000928:Antidepressive Agents; D005473:Fluoxetine; D017367:Selective Serotonin Reuptake Inhibitors