Manipulations during the second, but not the first, week of life increase susceptibility to cocaine self-administration in female rats.

We compared the effects of manipulations during week 1 vs week 2 of life on the propensity to self-administer cocaine. Pups received daily subcutaneous saline injections, were handled briefly, or remained undisturbed during their respective treatment periods. Animals handled during the second week of life exhibited increased locomotor response to novelty when tested on postnatal day (PND) 48, compared to all other groups. Rats were implanted with jugular catheters on PND 70 and then given the opportunity to self-administer (0.125 mg/kg/infusion) cocaine for 5 consecutive days (1 h sessions). The dose was then raised to 0.25 mg/kg/infusion for 5 days and to 0.5 mg/kg/infusion for the final 5 days of testing. Only animals manipulated during the second week of life acquired drug-taking behavior. These effects were both stimulus- and gender-specific. Females handled during the second week of life acquired cocaine self-administration (SA) at the lowest dose, and females injected during the second week of life acquired at the intermediate dose. Males injected during the second week of life showed a similar, but more variable, drug-taking pattern. There were no group differences in serum corticosterone response to novelty, although relative to undisturbed animals and those manipulated in the first week of life, female animals manipulated during the second week of life had lower basal expression of hippocampal glucocorticoid receptor mRNA in adulthood. We conclude that the second week of life in the rodent is a sensitive period during which manipulations result in a more vulnerable phenotype for the acquisition of cocaine SA.