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Repeated neonatal maternal separation alters intravenous cocaine self-administration in adult rats
K Matthews1, T W Robbins, B J Everitt
1Department of Experimental Psychology, Cambridge University, UK.
Insights
Early life stress from maternal separation alters adult cocaine use in rats. Neonatal separation impacts cocaine self-administration differently in males and females, highlighting developmental and gender-specific effects on drug-taking behavior.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Developmental Psychology
Background:
- Early environmental factors significantly influence behavioral responses to psychostimulant drugs.
- Neonatal experiences, such as maternal separation, can have lasting effects on brain development and behavior into adulthood.
Purpose of the Study:
- To investigate the long-term effects of repeated brief maternal separations during the neonatal period on cocaine self-administration in adult rats.
- To determine if these effects are dose- and gender-dependent.
Main Methods:
- Lister hooded rats underwent a repeated maternal separation procedure (REMS) during the neonatal period.
- Adult rats were assessed for acquisition and maintenance of cocaine self-administration across different doses (0.05, 0.08, 0.5 mg/injection).
- Dose-effect functions for cocaine self-administration and sensitivity to dopamine receptor antagonists (eticlopride, SCH 23390) were evaluated.
Main Results:
- REMS rats exhibited altered acquisition and maintenance of cocaine self-administration, with effects varying by dose and gender.
- Acquisition was generally retarded at lower doses (0.05 mg/injection) but facilitated in females at 0.08 mg/injection.
- Adult REMS females self-administered more cocaine than controls at a specific dose, while males self-administered less, indicating significant gender-specific alterations.
Conclusions:
- Repeated neonatal maternal separation alters adult cocaine-taking behavior in a developmentally and gender-specific manner.
- These findings underscore the critical role of early life environment in shaping vulnerability to drug addiction.
- The observed effects of neonatal separation contrast with those reported for post-weaning isolation rearing.
Abstract:
Behavioural responses to psychostimulant drugs can be profoundly affected by early environmental influences. The aim of this study was to describe the effects of repeated brief separations of rat pups from their dams during the early neonatal period on cocaine self-administration behaviour as adults. Lister hooded rats exposed to a repeated maternal separation procedure (REMS) showed altered acquisition and maintenance of cocaine self-administration as adults, the effects being dose and gender-dependent. Overall, the patterns of acquisition of self-administration across three doses of cocaine (0.05, 0.08 and 0.5 mg/injection) suggested a rightward shift in the acquisition dose-effect functions for the REMS animals relative to control animals. At 0.05 mg/injection, there was a retarded acquisition of cocaine self-administration in male and female neonatally separated rats. At 0.08 mg/injection there was a facilitated acquisition in female neonatally separated subjects. After establishment of stable self-administration of the training dose, in the same cohort of subjects, rightward and downward shifts in the cocaine self-administration dose-effect functions were determined for female and male REMS subjects, respectively, relative to their controls. The dose-effect function for both female groups was shifted to the left of that of the respective male groups, although the lighter body weights of the females meant that they administered a higher unit dose per unit body weight than the males. Whereas male REMS subjects tended to self-administer less cocaine than the controls at the dose eliciting maximal responding (0.03 mg/injection) and to make fewer lever responses overall at each dose tested, female REMS subjects self-administered significantly more cocaine than their respective controls at a dose of 0.03 mg/injection. There was no differential sensitivity to the rate-altering effects of the selective dopamine D2 receptor antagonist, eticlopride, or to the selective dopamine D1 receptor antagonist, SCH 23390. These data provide further evidence that altered early environment affects drug-taking behaviour in a developmentally specific and gender-specific manner, with the effects of neonatal separation contrasting with previously published data on the effects of post-weaning isolation rearing.