Behavioral, Neural, and Molecular Mechanisms of Conditioned Mate Preference: The Role of Opioids and First Experiences of Sexual Reward

Abstract

Although mechanisms of mate preference are thought to be relatively hard-wired, experience with appetitive and consummatory sexual reward has been shown to condition preferences for partner related cues and even objects that predict sexual reward. Here, we reviewed evidence from laboratory species and humans on sexually conditioned place, partner, and ejaculatory preferences in males and females, as well as the neurochemical, molecular, and epigenetic mechanisms putatively responsible. From a comprehensive review of the available data, we concluded that opioid transmission at μ opioid receptors forms the basis of sexual pleasure and reward, which then sensitizes dopamine, oxytocin, and vasopressin systems responsible for attention, arousal, and bonding, leading to cortical activation that creates awareness of attraction and desire. First experiences with sexual reward states follow a pattern of sexual imprinting, during which partner- and/or object-related cues become crystallized by conditioning into idiosyncratic “types” that are found sexually attractive and arousing. These mechanisms tie reward and reproduction together, blending proximate and ultimate causality in the maintenance of variability within a species.

From distal to proximal to interactive: Behavioral and brain synchrony during attraction, courtship, and sexual interaction

“…Consummatory behaviors are driven further by these systems (e.g., from phasic to tonic mesolimbic DA release) and the reward value of consummation is experienced concomitantly with a much larger release of opioids, followed by a period of satiety that is driven by serotonin's activation of descending prefrontal cortical inhibition. Opioids also have the ability to sensitize both dopamine and oxytocin systems through a molecular cascade that results in augmented synthesis and release of both neurotransmitters (Quintana, Mac Cionnaith, & Pfaus, 2022).…”

“…The brain contains primary neural systems to allow this, including mirroring systems in the cortex and hippocampus that underlie mimicked facial responses, limb and digit movements, and vocalizations, allowing the infant to practice connecting facial and other motor movements to particular emotions, thus creating motor "phonemes" for complex emotional experiences and the transgenerational expression of those experiences. It is likely also that synchronous behaviors, especially the mimicking of facial expressions and maintenance of eye contact, are also mediated by the integration of brain dopamine and oxytocin systems, and reinforced and sensitized by opioid actions on those systems (Loth & Donaldson, 2021;Quintana, Mac Cionnaith, & Pfaus, 2022).…”

“…There may be expectations of quick establishment, especially if there is some degree of similarity between the individual and the new partner (Brumbaugh & Fraley, 2007) or if the desire to do so is so great that distal or proximal flirtations are misinterpreted as signals of closeness. This is likely to occur due to another role of opioids in sensitizing oxytocin neurons to partner-related cues signaled by dopamine (Quintana, Mac Cionnaith, & Pfaus, 2022). The depression due to the loss of a partner can be in some sense assuaged by the introduction of a new partner (Brumbaugh & Fraley, 2015).…”

“…Orgasm-related sexual pleasure and reward mechanisms involve opioid sensitization of dopamine and oxytocin systems (Pfaus et al, 2012;Quintana, Mac Cionnaith, & Pfaus, 2022). This likely increases both nonverbal and verbal synchrony between partners, and further reinforces trust and connectedness, perhaps to the point of feeling a "merging of souls" during and after sex.…”

The effect of morphine on rat microglial phagocytic activity: an in vitro study of brain region-, plating density-, sex-, morphine concentration-, and receptor-dependency

“…Opioids have long been used for clinical pain management, but also have addictive properties (Agmo and Gómez 1991, Paredes 2014, Quintana, Mac Cionnaith et al 2022) that have contributed to the ongoing opioid epidemic (Terplan 2017, Stoicea, Costa et al 2019). The opioid morphine binds to both opioid receptors, which are present on several different cell types, and Toll-like Receptor 4 (TLR4), which is enriched on immune cells (Wang, Loram et al 2012, Xie, Gomes et al 2017).…”