Neuroplasticity in the Mesolimbic System Induced by Natural Reward and Subsequent Reward Abstinence

Kyle K. Pitchers, Margaret E. Balfour, Michael N. Lehman, Neil M. Richtand, Lei Yu, Lique M. Coolen

Research output: Contribution to journalArticlepeer-review

89 Scopus citations


Background: Natural reward and drugs of abuse converge on the mesolimbic system, where drugs of abuse induce neuronal alterations. Here, we tested plasticity in this system after natural reward and the subsequent impact on drug responses. Methods: Effects of sexual experience in male rats on behavioral sensitization and conditioned place preference associated with d-amphetamine (AMPH) and Golgi-impregnated dendrites and spines of nucleus accumbens (NAc) cells were determined. Moreover, the impact of abstinence from sexual behavior in experienced males on these parameters was tested. Results: First, repeated sexual behavior induced a sensitized locomotor response to AMPH compared with sexually naive control subjects observed 1, 7, and 28 days after last mating session. Second, sexually experienced animals formed a conditioned place preference for lower doses of AMPH than sexually naive males, indicative of enhanced reward value of AMPH. Finally, Golgi-Cox analysis demonstrated increased numbers of dendrites and spines in the NAc core and shell with sexual experience. The latter two alterations were dependent on a period of abstinence of 7-10 days. Conclusions: Sexual experience induces functional and morphological alterations in the mesolimbic system similar to repeated exposure to psychostimulants. Moreover, abstinence from sexual behavior after repeated mating was essential for increased reward for drugs and dendritic arbors of NAc neurons, suggesting that the loss of sexual reward might also contribute to neuroplasticity of the mesolimbic system. These results suggest that some alterations in the mesolimbic system are common for natural and drug reward and might play a role in general reinforcement.

Original languageEnglish (US)
Pages (from-to)872-879
Number of pages8
JournalBiological Psychiatry
Issue number9
StatePublished - May 1 2010
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biological Psychiatry


  • Dendritic spine
  • dopamine
  • nucleus accumbens
  • psychostimulant
  • sexual behavior
  • substance abuse


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