Sexual satiety modifies methamphetamine-induced locomotor and rewarding effects and dopamine-related protein levels in the striatum of male rats

Psychopharmacology (Berl). 2023 Apr;240(4):797-812. doi: 10.1007/s00213-023-06322-w. Epub 2023 Feb 6.

Abstract

Rationale: Drug and natural rewarding stimuli activate the mesolimbic dopaminergic system. Both methamphetamine (Meth) and copulation to satiety importantly increase dopamine (DA) release in the nucleus accumbens (NAc), but with differences in magnitude. This paper analyzes the interaction between Meth administration and the intense sexual activity associated with sexual satiety.

Objectives: To evaluate possible changes in Meth-induced behavioral effects and striatal DA-related protein expression due to sexual satiety.

Methods: Meth-induced locomotor activity and conditioned place preference (CPP) were tested in sexually experienced male rats that copulated to satiety (S-S) or ejaculated once (1E) the day before or displayed no sexual activity (control group; C). DA receptors and DA transporter expression were determined by western blot in the striatum of animals of all sexual conditions treated with specific Meth doses.

Results: Meth's locomotor and rewarding effects were exacerbated in S-S animals, while in 1E rats, only locomotor effects were enhanced. Sexual activity, by itself, modified DA-related protein expression in the NAc core and in the caudate-putamen (CPu), while Meth treatment alone changed their expression only in the NAc shell. Meth-induced changes in the NAc shell turned in the opposite direction when animals had sexual activity, and additional changes appeared in the NAc core and CPu of S-S rats.

Conclusion: Sexual satiety sensitizes rats to Meth's behavioral effects and the Meth-induced striatal DA-related protein adaptations are modified by sexual activity, evidencing cross-sensitization between both stimuli.

Keywords: Caudate-putamen; Conditioned place preference; Dopamine receptors; Dopamine transporter; Hyperlocomotion; Male sexual behavior; Mesolimbic system; Methamphetamine; Natural and drug rewards; Nucleus accumbens.

MeSH terms

  • Animals
  • Corpus Striatum
  • Dopamine / metabolism
  • Male
  • Methamphetamine*
  • Neostriatum / metabolism
  • Nucleus Accumbens
  • Rats

Substances

  • Methamphetamine
  • Dopamine