Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats

Exp Clin Psychopharmacol. 2007 Feb;15(1):48-57. doi: 10.1037/1064-1297.15.1.48.


Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Analysis of Variance
  • Animals
  • Conditioning, Operant / drug effects
  • Discrimination Learning / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Male
  • Memory / drug effects
  • Muscarinic Antagonists / administration & dosage
  • Muscarinic Antagonists / pharmacology
  • Orchiectomy
  • Psychomotor Performance / drug effects
  • Rats
  • Rats, Long-Evans
  • Scopolamine / administration & dosage
  • Scopolamine / pharmacology*
  • Testosterone Propionate / administration & dosage
  • Testosterone Propionate / pharmacology*


  • Muscarinic Antagonists
  • Scopolamine
  • Testosterone Propionate