Cytisine and diarylpropionitrile may not modulate depressive behaviors in female WKY rats

Abstract

Listen

Translate article

Event Abstract Back to Event Cytisine and diarylpropionitrile may not modulate depressive behaviors in female WKY rats Praveen Kandi1, Joseph Tanga1 and Renee L. Hayslett1* 1 Mercer University, College of Pharmacy and Health Sciences, United States Nicotine and estrogen may regulate mood and influence depressive behaviors. Results from rodent studies suggest the potential involvement of nicotinic cholinergic receptors and estrogen receptors in antidepressant-like behavior. Specifically, blockade of nicotinic receptors containing the β2 subunit may be responsible for antidepressant effects [1]. Furthermore, selective estrogen receptor β (ERβ) agonists have been shown to reduce depressive behaviors in female ovariectomized rats [2]. In this study, we evaluated potential anti-anxiety and anti-depressant effects of a nicotinic agent, cytisine, and a selective estrogen receptor modulator, diarylpropionitrile (DPN), in an animal model of depression in female rats. Cytisine is a partial agonist at α4β2 receptors and a full agonist at α3β4 and α7 receptors. DPN is a selective ERβ agonist. The Wistar Kyoto (WKY) rat strain is a putative model of endogenous depression. Compared to their control, the Wistar rat, WKY rats demonstrate hormonal, behavioral and physiological parameters that are similar to symptoms found in depressed patients [3]. WKY rats appear to be resistant to standard SSRI antidepressants. Interestingly, a subset of depressed patients does not respond to SSRI drugs. Therefore, this model could be useful in identifying novel agents for antidepressant therapy. Female WKY and Wistar rats (n=6-8/group) received subcutaneous injections of cytisine (0.5, 1, 1.5 mg/kg), DPN (10 μg, 0.5 mg/kg, 1 mg/kg) or vehicle prior to being tested in the elevated plus maze (EPM), locomotor activity chamber (LCA) and forced swim test (FST). Dosages and latencies for drug administration were chosen based on previous reports and data from preliminary studies. Our results show that WKY rats displayed significantly more depressive behaviors compared to Wistar rats. WKY rats had significantly more immobility counts and also significantly less locomotor activity compared to Wistar rats. No differences were detected in the EPM with cytisine or DPN in either strain. In addition, none of the doses of DPN produced significant effects on behavior in the other tested paradigms. Because the rats had intact reproductive systems, their behavior could be influenced by the estrous cycle. At the tested doses of cytisine, the 1.5 mg/kg dose significantly increased immobility in the FST in Wistar and WKY rats. There was a trend for WKY rats treated with 1.5 mg/kg of cytisine to exhibit reduced locomotor activity; however, this did not reach statistical significance. At this dose of cytisine there appears to be an exaggeration of depressive behaviors. This observation could be due to activation of nicotinic receptors in the peripheral ganglia, which may cause autonomic dysregulation and account for the decrease of locomotor activity and increase in immobility in the FST. In conclusion, cytisine and DPN do not appear to have anti-anxiety or anti-depressant effects in the female WKY rat. Additional experiments that test a wider range of doses, combination of drugs, and consider the phase of estrous cycle are necessary.