Preadolescent drd1-EGFP mice exhibit cocaine-induced behavioral sensitization

Abstract

In adult mice, repeated cocaine administration induces behavioral sensitization measured as increased horizontal locomotor activity. Cocaine-induced locomotor sensitization has been well characterized in adult mice. In adult animals, the D1 dopamine receptor is important for mediating effects of cocaine. The effect of cocaine on D1 receptor expression and function in preadolescent animals is less understood. The recently described drd1-Enhanced Green Fluorescent Protein (drd1-EGFP) reporter mouse is a useful model for performing such mechanistic studies; however, preadolescent drd1-EGFP mice have not been characterized previously. Here we studied cocaine-induced locomotor sensitization in preadolescent drd1-EGFP reporter mice. We administered 15 mg/kg cocaine three times daily at one hour intervals for seven consecutive days beginning on postnatal day 23 to drd1-EGFP reporter mice and the commonly used C57BL/6 mice. Under this regimen, preadolescent mice of both strains exhibited cocaine-induced locomotor sensitization; however, by day 7 the cocaine-induced locomotor activity in the drd1-EGFP mice was maintained for a longer duration compared to the C57BL/6 mice. The preadolescent drd1-EGFP mice also exhibited elevated basal locomotor activity in a novel environment and had higher D1 and D2 dopamine receptor mRNA levels in the caudate nucleus compared to the C57BL/6 mice. The cocaine-induced locomotor sensitization was not retained when the drd1-EGFP mice were maintained cocaine-free for two weeks suggesting that in preadolescent drd1-EGFP mice the cocaine-induced changes do not persist.

A DRD1 Polymorphism Predisposes to Lung Cancer among Those Exposed to Secondhand Smoke during Childhood

“…Indeed, a recent Surgeon’s General report concluded that children exposed to parental smoke have higher risk of lower respiratory tract illnesses (2) and studies of long-term exposures starting at different time points in the life-course have shown that the earlier the exposure is encountered, the greater the tumor incidence that ensues (37). Interestingly, several recent studies also point to a role for pre-natal and early-life exposures in the modulation of DRD1 expression and function later in life (38, 39). As to how the pathobiological memory of an early-life exposure is maintained into adult life is largely unknown, but epigenetic modifications are one possibility (40–42).…”

Post‐transcriptional regulation of dopamine D1 receptor expression in caudate‐putamen of cocaine‐sensitized mice

“…We have previously described the drd1 ‐EGFP mice (Tg(Drd1‐a‐EGFP)X60Gsat/Mmmh MMRRC:000297) used in this study (Tobón & Kuzhikandathil, ). The drd1 ‐EGFP transgenic mice have a mixed Swiss Webster/FVB genetic background.…”

“…We have previously described the binge administration protocol used in this paper (Tobón & Kuzhikandathil, ). Briefly, beginning on P23, mice received three daily intraperitoneal (i.p.)…”

“…We have previously described the methods for measuring the horizontal locomotor activity using the open field photobeam activity system (PAS; SD Instruments, San Diego, CA, USA) (Tobón & Kuzhikandathil, ). The animals were placed in the open field arena for 30 min prior to injections, for habituation.…”

“…Brain tissue was harvested and stored as described previously (Tobón et al ., ; Tobón & Kuzhikandathil, ). Briefly, whole brain was isolated and immersed in ice‐cold saline.…”