The conditioned response erection (CRE)—a new approach to modelling erectile responses in the rat

Abstract

Several animal models are currently used in erectile (dys)function research; these models fail to account for the conditions involving the more spontaneous erections in humans. Recently, we observed an increase in the number of ‘spontaneously’ occurring erections in rats with previous exposure to apomorphine (APO), a centrally acting drug that initiates penile erections and yawns. Based on this observation, we designed a series of experiments to characterize the development of enhanced, non-apomorphine-induced erections or ‘spontaneous’ erectile responses to vehicle administration in rats with previous exposure to APO. We further examined the effects of castration on these conditioned erections.

Naïve (ie never received APO) rats were administered vehicle (1 ml/kg saline) to determine the frequency of baseline erections and yawns. An alternating series of APO (80 μg/kg s.c.) and vehicle administrations were performed over several days and subsequent erectile and yawning responses were recorded. Following 3 sets of 3 APO administrations (with vehicle administered between sets), and the 3rd vehicle administration, these rats were then surgically castrated and allowed 30 days to recover. Following this, APO was administered 3 times to determine erectile and yawning responses post-castration, followed by vehicle administration to determine the effects of castration on conditioned APO responses.

The major findings were: (1) that although naïve rats had a basal spontaneous erectile response (0.75±0.88; 4 of 8 rats with at least one erection), repetitive administration (up to 22 treatments) of the central initiator apomorphine significantly increased the number of erections (1.8±0.7; 7 of 8 rats with at least one erection) and yawning (2.5±2.47) responses to vehicle administration; and (2) both spontaneous yawning and erectile responses were found to be androgen dependent since castration dramatically lowered the number of erections (0.13±0.35; 1 of 8 rats with at least one erection) and yawns (0). Therefore, this method of producing erections without a pharmacological manipulation provides an additional animal model which can be used in conjunction with the APO-induced erections in characterizing the physiology and pathophysiology of erectile function in conscious rats.