Comment: The significance of this study is explained in this science article: The Amount Of Sex You Have May Determine How Vulnerable You Are To Drug Addiction (reproduced here, followed by the underlying research).
Your sensitivity to certain drugs may be determined by the amount of sex you have, which could partially explain why some people are more susceptible to addiction than others. More specifically, those who have lots of sex may be at risk of developing a tolerance to some drugs, although when these people hit a rough patch in their love lives and experience too many lonely nights, their sensitivity to these substances can dramatically increase.
As is often the case with experiments involving illegal substances, the study that gave rise to these conclusions was conducted on rats rather than people. Publishing their findings in the Journal of Neuroscience, the researchers attempt to build on previous work that has shown that when rats are over-sexed, the dopamine-releasing neurons in a part of the brain called the ventral tegmental area (TVA) shrink.
Since the TVA is part of the brain’s reward circuit, it is largely responsible for generating feelings of pleasure, so when these neurons are diminished, so too are these gratifying sensations. Interestingly, a similar effect is seen in opiate addicts, many of whom therefore build up a tolerance to their drug of choice. Likewise, overly promiscuous rats have been found to show a level of tolerance to drugs like amphetamine, requiring larger doses in order to satisfy their need for a buzz.
In the latest study, the researchers allowed rats to mate to their heart’s content, before then forcing them to remain celibate for a period of time. Following this abstinent interlude, the rats began to show an increased sensitivity for amphetamines, craving the drug and displaying a high vulnerability for addiction.
To figure out what drives this effect, the researchers chemically blocked the activity of VTA dopamine neurons while allowing the rats to mate like rabbits, before once again forcing them to remain abstinent for a week. This time, they found that having sex had no effect on the size of these neurons, and therefore caused no changes to the rats’ sensitivity to amphetamines.
The study authors note that blocking dopamine during sex suppressed the expression of a transcription factor called ΔFosB, which they suspect may be responsible for the changes in neuronal plasticity that are seen under normal conditions.
As such, they conclude that the activation of dopamine neurons in the TVA during sex results in changes to neuron size and sensitivity, which, when followed by a period of abstinence, causes rats – and possibly people – to become particularly receptive to the effects of certain drugs, therefore increasing their susceptibility to addiction.
Ventral Tegmental Area Dopamine Cell Activation during Male Rat Sexual Behavior Regulates Neuroplasticity and d-Amphetamine Cross-Sensitization following Sex Abstinence
Journal of Neuroscience
21 September 2016, 36 (38) 9949-9961; DOI: https://doi.org/10.1523/JNEUROSCI.0937-16.2016
Abstract
Experience with sexual behavior causes cross-sensitization of amphetamine reward, an effect dependent on a period of sexual reward abstinence. We previously showed that ΔFosB in the nucleus accumbens (NAc) is a key mediator of this cross-sensitization, potentially via dopamine receptor activation. However, the role of mesolimbic dopamine for sexual behavior or cross-sensitization between natural and drug reward is unknown. This was tested using inhibitory designer receptors exclusively activated by designer drugs in ventral tegmental area (VTA) dopamine cells. rAAV5/hSvn-DIO-hm4D-mCherry was injected into the VTA of TH::Cre adult male rats. Males received clozapine N-oxide (CNO) or vehicle injections before each of 5 consecutive days of mating or handling. Following an abstinence period of 7 d, males were tested for amphetamine conditioned place preference (CPP). Next, males were injected with CNO or vehicle before mating or handling for analysis of mating-induced cFos, sex experience-induced ΔFosB, and reduction of VTA dopamine soma size. Results showed that CNO did not affect mating behavior. Instead, CNO prevented sexual experience-induced cross-sensitization of amphetamine CPP, ΔFosB in the NAc and medial prefrontal cortex, and decreases in VTA dopamine soma size. Expression of hm4D-mCherry was specific to VTA dopamine cells and CNO blocked excitation and mating-induced cFos expression in VTA dopamine cells. These findings provide direct evidence that VTA dopamine activation is not required for initiation or performance of sexual behavior. Instead, VTA dopamine directly contributes to increased vulnerability for drug use following loss of natural reward by causing neuroplasticity in the mesolimbic pathway during the natural reward experience.
SIGNIFICANCE STATEMENT Drugs of abuse act on the neural pathways that mediate natural reward learning and memory. Exposure to natural reward behaviors can alter subsequent drug-related reward. Specifically, experience with sexual behavior, followed by a period of abstinence from sexual behavior, causes increased reward for amphetamine in male rats. This study demonstrates that activation of ventral tegmental area dopamine neurons during sexual experience regulates cross-sensitization of amphetamine reward. Finally, ventral tegmental area dopamine cell activation is essential for experience-induced neural adaptations in the nucleus accumbens, prefrontal cortex, and ventral tegmental area. These findings demonstrate a role of mesolimbic dopamine in the interaction between natural and drug rewards, and identify mesolimbic dopamine as a key mediator of changes in vulnerability for drug use after loss of natural reward.