Effects of environmental enrichment upon ethanol-induced conditioned place preference and pre-frontal BDNF levels in adolescent and adult mice

Abstract

Environmental enrichment (EE) provides a non-pharmacological tool to alter drug-induced reward, yet its effects on ethanol-induced reward remain controversial. We analyzed adolescent vs. adult (mice) differences in the influence of EE on ethanol-induced conditioned place preference (CPP). The effects of these treatments on brain-derived neurotrophic factor (BDNF) levels in the prefrontal cortex were examined in a separate group of animals. Ethanol-induced CPP was found in adults, and it was similar in EE and in animals reared under standard housing conditions (SC). Adolescents kept under EE, but not those in SC, exhibited CPP. Among SC, but not among EE, adolescents, BDNF levels were significantly lower in those treated with ethanol than in those given vehicle. These results indicate that, compared to adults, adolescent exhibited reduced sensitivity to ethanol's rewarding effects, yet the youth but not the adults exhibited sensitivity to the promoting effect of EE upon CPP by ethanol. Ethanol significantly reduced BDNF levels in adolescents reared under standard housing conditions, but not in adult mice nor in adolescents given EE housing conditions. The present results add to the plethora of adolescent-specific responses to ethanol or to environmental stimuli that may put the youth at risk for escalation of ethanol intake.

Figure 1

Adolescent and adult mice under environmental enrichment conditions were housed in large transparent polycarbonate cages (42 cm length × 28 cm width × 21.5 cm height) equipped with seven objects and toys, including a running wheel, ladders, pipes and house-like objects. One of the objects was a round container that contained food. The placement and composition of these non-chewable plastic objects were changed every week to prevent habituation. The photograph illustrates one of these compositions.

Figure 2

Ethanol-induced conditioned place preference (CPP) in adolescent male Swiss mice, at test sessions 1, 2, 3 and 4. The line graphs depict time spent (in seconds or in percent preference, sections (A) and (C), respectively) in the chamber associated with ethanol’s effects (conditioned stimulus [CS⁺]), as a function of rearing condition (standard [control] conditions and environmental enrichment; SC and EE groups, respectively) and treatment during CPP training (vehicle or 2.0 g/kg ethanol). The small bar graphs (B and D) depict absolute (s) and percent time spent in the CS⁺ collapsed across test sessions. Animals that were given ethanol and were reared under EE conditions spent significantly more time in the chamber associated with ethanol than the rest of the animals that were treated with vehicle or ethanol, an effect that was statistically similar across test sessions. This significant effect is indicated by the asterisk sign. Values express mean ± SEM.

Figure 3

Ethanol-induced conditioned place preference (CPP) of adult male Swiss mice, at test sessions 1, 2, 3 and 4. The line graphs depict time spent (in seconds or in percent preference, sections (A) and (C), respectively) in the chamber associated with ethanol’s effects (conditioned stimulus [CS⁺]), as a function of rearing condition (standard [control] conditions and environmental enrichment; SC and EE groups, respectively) and treatment during CPP training (vehicle or 2.0 g/kg ethanol). The small bar graphs (B and D) depict absolute (s) and percent time spent in the CS⁺ collapsed across test sessions. Animals that were given ethanol spent significantly more time in the chamber associated with ethanol than animals that were treated with vehicle, an effect that was statistically similar across test sessions and in EE and SC subjects. This significant effect is indicated by the asterisk sign. Values express mean ± SEM.

Figure 4

Brain-derived neurotrophic factor (BDNF) levels in prefrontal cortex of adolescent and adult male Swiss mice as a function of rearing condition (standard [control] conditions and environmental enrichment) and treatment (4, every-other-day administrations of 0.0 [vehicle control] or 2.0 g/kg ethanol). The adolescent group treated with ethanol and exposed to standard (control) rearing conditions (first black bar on the left) exhibited significantly less BDNF levels than (A) any of the other groups (adolescents or adults) reared under standard housing conditions and treated with vehicle [these significant differences are indicated by the pound (#) and currency ($) signs, respectively], (B) the adults treated with ethanol and exposed to standard (control) rearing conditions [a significant difference indicated by the ampersand (&) sign] and C) adolescents reared under environmental enrichment conditions and treated with ethanol. The latter significant difference is are indicated by the asterisk (*) sign. Values express mean ± SEM.

Figure 5

Body weight (g, mean ± SEM) of male Swiss mice, prior to every administration of saline or ethanol (sessions 1 to 8) and prior to the habituation session, as a function of Age (adolescents or adults), Environmental condition (environmental enriched [EE] or standard housing conditions [SC]) and Treatment (4, every-other-day administrations of 0.0 [vehicle control] or 2.0 g/kg ethanol). The asterisk sign indicates that, throughout days, body weight was significantly lower in EE adolescent animals than in SC counterparts. The pound sign indicates a significant difference between EE adults given ethanol and vehicle, SC adults, during habituation and sessions 1 and 2.