Abstract
The aim of this study was to determine whether manipulation of weaning time and of social variables during prepuberty in mice would account for the individual features of behavior that are correlated with the abuse of drugs. This issue was addressed by searching for differences in cocaine effects in the adult offspring of both sexes from outbred Swiss CD-1 mouse litters. On Postnatal Day 15, litters were split into two halves, with one half litter weaned (precocious weaning, PW) while the other remained with the dam (regular weaning, RW). At the same time, pups in each half litter were assigned to either a unisex or a mixed-sex rearing condition. From Postnatal Day 25 to adulthood (time of testing, 70 days), all mice were rehoused according to both sex and weaning. Both adult PW male mice and unisex-reared animals of both sexes were, in general, more active than corresponding controls. In a place-conditioning schedule, aimed at assessing the reinforcing properties of cocaine HCl (two drug pairings; 0, 1, or 5 mg/kg, i.p.), mixed-sex mice of both sexes were readily conditioned by the drug. Time of weaning determined the direction of the conditioned performance. In fact, although RW mice in this specific paradigm showed a reduction of time spent in the drug-paired area, subjects weaned precociously developed a quite clear conditioned place preference in a dose-dependent fashion. Interestingly, irrespective of their weaning history, cocaine failed to induce conditioning in animals that had undergone sexual segregation during development. These differential cocaine effects (1) suggest alterations in the function of mesolimbic and nigrostriatal DA systems linked to subtle changes in social stimulation during development, and (2) may be associated with an acquired predisposition to exhibit an individual responsivity to drugs of abuse.
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This research was supported as a prosecution of the Subproject on Behavioral Pathophysiology (Project on Noninfectious Pathology) supported by the Istituto Superiore di Sanità, Rome, Italy, and by the Italian National Health Service project “Risk factors in maternal and child health.”
We acknowledge Flavia Chiarotti for her expert statistical advice and the help of Carla Tascone in formatting the manuscript.
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Laviola, G., Dell’omo, G. Precocious weaning and changes in social variables during prepuberty affect cocaine reinforcing properties in adult mice. Psychobiology 25, 163–170 (1997). https://doi.org/10.3758/BF03331923
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DOI: https://doi.org/10.3758/BF03331923