Reduction of cocaine-induced locomotor effects by enriched environment is associated with cell-specific accumulation of DeltaFosB in striatal and cortical subregions (2016)

Int J Neuropsychopharmacol. 2016 Nov 4. pii: pyw097. doi: 10.1093/ijnp/pyw097.

Lafragette A1,2, Bardo MT3, Lardeux V1,2, Solinas M1,2, Thiriet N4,2.



Early exposure to enriched environments (EE) has been shown to decrease the locomotor effects induced by repeated injections of cocaine and to modify basal and cocaine-induced total protein levels of the transcription factor delta-FosB (ΔFosB) in the whole striatum of mice. In this study, we aimed at characterizing whether the profile of ΔFosB accumulation induced by EE and cocaine would be similar or different in terms of brain areas and cell type.


We used mice expressing the eGFP protein in D1 receptor positive (D1R(+)) neurons to determine whether ΔFosB induced by EE or cocaine injections (5X15mg/kg) would occur in selective sub-populations of neurons in several sub-regions of the striatum and prefrontal cortex.


We found that: 1) exposure to EE reduces cocaine-induced locomotor activation, confirming our previous findings; 2) exposure to EE by itself increases the accumulation of ΔFosB mostly in D1R(-) cells in the shell part of the nucleus accumbens (NAc) and dorsal striatum (DSt), whereas in the NAc Core, ΔFosB accumulates in both D1R(+) and D1R(-) neurons; 3) in standard environment (SE) mice, cocaine induces accumulation of ΔFosB selectively in D1R(+) cells in the NAc, DSt and infralimbic cortex; 4) the effects of EE and cocaine on accumulation of ΔFosB were reciprocally blocked by their combination.


Altogether, these results suggest that the EE-induced reduction in behavioral effects of cocaine might result from two distinct effects on ΔFosB in striatal medium-sized spiny neurons belonging to the direct and the indirect pathways.

KEYWORDS:  Enriched environment; behavioral sensitization; cocaine; medium-sized spiny neurons; ΔFosB

PMID: 27815415

DOI: 10.1093/ijnp/pyw097