A novel approach for predicting antidepressant-induced sexual dysfunction in rats.
BACKGROUND
Sexual dysfunction is associated with antidepressant discontinuation. Therefore, there is a need for models that predict antidepressant-induced sexual dysfunction.


OBJECTIVE
To develop a predictive method for evaluating antidepressant-induced sexual dysfunction.


METHODS
Male Sprague-Dawley rats were allowed access to sexually receptive females during a single overnight mating session and then treated with antidepressants known to produce differing levels of sexual dysfunction in the clinic. Two to three weeks later, following either acute, subchronic (7-day), or chronic (14-day) antidepressant treatment, rats were observed for penile erections (PE) in the presence of sexually receptive females that were not accessible for contact but served as visual, auditory, and olfactory stimuli in the testing area.


RESULTS
Chronic treatment of fluoxetine (10 mg/kg), desipramine (10 mg/kg), and bupropion (20 mg/kg) reduced the number of PE 71, 53, and 8%, respectively, relative to vehicle-treated rats. This rank order of the compounds' propensity for reducing PE is comparable to the rank order of the compounds' ability to produce sexual dysfunction during antidepressant treatment in the clinic. Additionally, drugs used to treat antidepressant-induced sexual dysfunction in the clinic, such as sildenafil, yohimbine, and dopamine agonists, were also effective in attenuating the deficits in the number of noncontact PE produced by chronic fluoxetine treatment.


CONCLUSIONS
Taken together, this model represents a novel approach for predicting antidepressant-induced sexual dysfunction in rats, which parallels the pattern of reports of sexual dysfunction in the clinic associated with different antidepressant treatments and the ability of adjunct treatment to reverse the sexual impairments produced by antidepressants.
Sukoff Rizzo
Stacey J
SJ
Depression and Anxiety Research, Discovery Neuroscience, Wyeth Research, CN 8000, Princeton, NJ 08543-8000, USA. rizzos@wyeth.com
Schechter
Lee E
LE
Rosenzweig-Lipson
Sharon
S
D000818:Animals; D000928:Antidepressive Agents / Q000633:toxicity*; D016642:Bupropion / Q000633:toxicity; D003891:Desipramine / Q000633:toxicity; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000494:pharmacology; D005473:Fluoxetine / Q000633:toxicity; D008134:Long-Term Care; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
D000928:Antidepressive Agents; D018491:Dopamine Agonists; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D014665:Vasodilator Agents; D005473:Fluoxetine; D016642:Bupropion; D015016:Yohimbine; D000068677:Sildenafil Citrate; D003891:Desipramine