Conditioned odor aversion induces social anxiety towards females in wild‐type and TrpC2 knockout male mice

Abstract

Female-emitted pheromonal inputs possess an intrinsic rewarding value for conspecific males, promoting approach and investigation of the potential mating partner. In mice these inputs are detected mainly by the vomeronasal organ (VNO) and the main olfactory epithelium (MOE). We investigated the role of VNO-mediated inputs in experience-dependent plasticity of reproductive responses. We applied a sex-specific conditioned odor aversion (COA) paradigm on adult, wild-type (WT) male mice and on male mice impaired in VNO-mediated signal transduction (TrpC2 ). We found that WT males, which underwent COA to female-soiled bedding, lost their innate preference to female odors and presented lower motivation to approach a sexually receptive female. COA also abolished the testosterone surge normally seen following exposure to female odors. Moreover, the conditioned males displayed impairments in copulatory behaviors, which lasted for several weeks. Surprisingly, these males also exhibited phobic behaviors towards receptive females, including freezing and fleeing responses. In contrast, WT males which underwent COA specifically to male pheromones showed no change in olfactory preference and only a marginally significant elevation in intermale aggression. Finally, we show that TrpC2 males were able to acquire aversion to female-soiled bedding and presented similar behavioral alterations following COA in their responses to female cues. Our results demonstrate that the intrinsic rewarding value of female pheromones can be overridden through associative olfactory learning, which occurs independently of VNO inputs, probably through MOE signaling.

The role of transient receptor potential channels in joint diseases

“…-/-· altered responses to pheromones TRPC2 is not functionally expressed in humans Beny and Kimchi, 2016;Desai and Clapham, 2005;Leypold et al, 2002;Stowers et al, 2002;Wu et al, 2014 TRPC3 -/-· defective normal functioning of the hind paws · no effect on agonist-mediated vasoconstriction or nonspecific depolarisation · decreased behavioral manifestations of seizures H a r t m a n n e t a l . , 2 0 0 8 ; Kochukov et al, 2013;Phelan et al, 2017 …”

Nucleus Accumbens Dopamine Signaling Regulates Sexual Preference for Females in Male Mice

“…Dopamine (DA) release in the nucleus accumbens (NAc) was suggested to be involved in mediating sexual motivation and behavior (Brom et al, 2014;Pfaus and Phillips, 1991). Specifically, female urine or female-soiled bedding, considered to be sources of pheromones (Choi et al, 2005;Isogai et al, 2011), have been shown to be intrinsically rewarding and strongly attractive to males (Ago et al, 2015;Beny and Kimchi, 2016;Malkesman et al, 2010). These pheromone sources were also shown to activate the mesolimbic DA system, even prior to expression of copulatory behavior (Kim et al, 2015;Malkesman et al, 2010;Robinson et al, 2001), and can serve as unconditioned natural reinforcers that induce associative learning Griffiths and Brennan, 2015).…”

Social recognition in rats and mice requires integration of olfactory, somatosensory and auditory cues

“…We used this protocol to show that rats and mice did not discriminate between fear-conditioned and neutral social stimuli if these animals were anesthetized either during the conditioning session or during the discrimination test, despite the unpleasant experience associated with the conditioned stimulus. Notably, a previous study employed a similar approach involving aversive conditioning to female odors showed that TrpC2 knockout mice could be conditioned to avoid female stimuli, despite their lack of innate discrimination between male and female stimuli 65 . Therefore, our SFC results clearly support the conclusions that mice and rats do not discriminate between anesthetized stimuli due to recognition failure, rather than because of problems with motivation.…”