Effects of perinatal exposure to delta 9-tetrahydrocannabinol on operant morphine-reinforced behavior.
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.
González
Begoña
B
Departamento de Psicobiología, Facultad de Psicología, Universidad Nacional de Educación a Distancia, Ciudad Universitaria, 28040 Madrid, Spain.
de Miguel
Rosario
R
Martín
Sonsoles
S
Pérez-Rosado
Alberto
A
Romero
Julián
J
García-Lecumberri
Carmen
C
Fernández-Ruiz
Javier
J
Ramos
José Antonio
JA
Ambrosio
Emilio
E
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D012054:Reinforcement, Psychology; D012727:Sex Characteristics
D009020:Morphine; D013759:Dronabinol; D004298:Dopamine