Effects of perinatal exposure to delta 9-tetrahydrocannabinol on operant morphine-reinforced behavior

Pharmacol Biochem Behav. 2003 Jun;75(3):577-84. doi: 10.1016/s0091-3057(03)00115-1.

Abstract

The present study examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) when administered during the perinatal period on morphine self-administration in adulthood. To this end, pregnant Wistar rats were daily exposed to Delta(9)-THC from the fifth day of gestation up to pup weaning, when they were separated by gender and left to mature to be used for analyses of operant food- and morphine-reinforced behavior in a progressive ratio (PR) schedule. We also analyzed dopaminergic activity (DOPAC/DA) in reward-related structures during specific phases of the behavioral study. In both reinforcement paradigms, food and morphine, females always reached higher patterns of self-administration than males, but this occurred for the two treatment groups, Delta(9)-THC or vehicle. These higher patterns measured in females corresponded with a higher DOPAC/DA in the nucleus accumbens prior to the onset of morphine self-administration in comparison to males. Interestingly, DOPAC/DA was lower in Delta(9)-THC-exposed females compared to oil-exposed females and similar to oil- and Delta(9)-THC-exposed males. In addition, Delta(9)-THC-exposed females also exhibited a reduction in DOPAC/DA in the ventral tegmental area, which did not exist in males. All these changes, however, disappeared after 15 days of morphine self-administration and they did not reappear after 15 additional days of extinction of this response. Our data suggest that females are more vulnerable than males in a PR schedule for operant food and morphine self-administration; perinatal Delta(9)-THC exposure is not a factor influencing this vulnerability. The neurochemical analysis revealed that the activity of limbic dopaminergic neurons prior to morphine self-administration was higher in females than males, as well as that the perinatal Delta(9)-THC treatment reduced the activity of these neurons only in females, although this had no influence on morphine vulnerability in these animals.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Conditioning, Operant / drug effects*
  • Conditioning, Operant / physiology
  • Dopamine / metabolism
  • Dronabinol / pharmacology*
  • Female
  • Male
  • Morphine / pharmacology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Reinforcement, Psychology*
  • Sex Characteristics

Substances

  • Morphine
  • Dronabinol
  • Dopamine