High ethanol dose during early adolescence induces locomotor activation and increases subsequent ethanol intake during late adolescence

Abstract

Adolescent initiation of ethanol consumption is associated with subsequent heightened probability of ethanol use disorders. The present study examined the relationship between motivational sensitivity to ethanol initiation in adolescent rats and later ethanol intake. Experiment 1 determined that ethanol induces locomotor activation shortly after administration but not if tested at a later post-administration interval. In Experiment 2, adolescent rats were assessed for ethanol-induced locomotor activation on postnatal Day 28. These animals were then evaluated for ethanol-mediated conditioned taste aversion and underwent a 16-day-long ethanol intake protocol. Ethanol-mediated aversive effects were unrelated to ethanol locomotor stimulation or subsequent ethanol consumption patterns. Ethanol intake during late adolescence was greatest in animals initiated to ethanol earliest at postnatal Day 28. Females that were more sensitive to ethanol's locomotor-activating effects showed a transient increase in ethanol self-administration. Blood ethanol concentrations during initiation were not related to ethanol-induced locomotor activation. Adolescent rats appeared sensitive to the locomotor-stimulatory effects of ethanol. Even brief ethanol exposure during adolescence may promote later ethanol intake.

Figure 1

Locomotor activity (forward locomotion and wall-climbing, left and right sections, respectively, expressed in seconds) in 28-day-old male and female adolescent rats as a function of ethanol treatment (0.0 [vehicle] or 2.5 g/kg) and post-administration bin of assessment (5–11 min or 30–36 min; early and late intervals, respectively). Data were collapsed across sex (male or female). The sex factor did not exert a significant main effect or significantly interact with the remaining variables. The vertical bars indicate SEM.

Figure 2

Upper panel: Locomotor activity during a post-administration time of 5–11 min (forward locomotion and wall-climbing, left and right sections, respectively, expressed in seconds) in 28-day-old male and female adolescent rats given ethanol (2.5 g/kg, i.g.) or its vehicle (tap water). Lower panel: Locomotor activity (forward-locomotion) during a post-administration time of 5–11 min in 28-day-old male and female adolescent rats given ethanol (2.5 g/kg, i.g.) or its vehicle (tap water). In this panel, ethanol-treated adolescents were divided into high- and low-responders by a split-median procedure. Data were collapsed across sex (male or female). The sex factor did not exert a significant main effect or significantly interact with the remaining variables. The vertical bars indicate SEM.

Figure 3

Saccharin intake (ml/100 g) during conditioning and test sessions in male and female adolescent rats as a function of ethanol treatment during initiation (PD28) and conditioning (PD31). On PD28, the rats were treated with ethanol (2.5 g/kg, i.g.) or its vehicle (tap water, 0.0 g/kg). During conditioning (PD31), saccharin intake was paired with ethanol administration (2.5 g/kg, i.g.) or its vehicle (tap water, 0.0 g/kg). The length of conditioning and test sessions was 30 and 60 min, respectively. Data were collapsed across sex (male or female). The sex factor did not exert a significant main effect or significantly interact with the remaining variables. The vertical bars indicate SEM.

Figure 4

Ethanol intake (grams per kilogram and its corresponding percentage, upper and lower sections, respectively) in male and female adolescent rats during Phases 1 and 4 of the ethanol intake protocol as a function of day of assessment (sessions 1, 2, 3, and 4) and ethanol treatment during initiation. Initiation occurred on PD28 and consisted of a single administration of ethanol (2.5 g/kg, i.g.) or its vehicle (0.0 g/kg, tap water). Then, during PD37–52, the adolescents were subjected to a procedure for the assessment of ethanol consumption, which consisted of four phases. The graph depicts ethanol intake during Phases 1 and 4. Each of these phases was composed of four sessions, in which animals had access to water and a given ethanol solution (3, 4, 5, or 6% ethanol, for sessions 1, 2, 3, and 4, respectively). Data were collapsed across sex. The sex factor did not exert a significant main effect or significantly interact with the remaining variables. The smaller bar graphs depict ethanol intake during Phases 1 and 4, averaged across sessions. The vertical bars indicate SEM.

Figure 5

Ethanol intake (g/kg) in female and male adolescent rats during Phase 2 of the intake protocol as a function of day of assessment (sessions 1, 2, 3, and 4) and ethanol treatment during initiation. Initiation occurred on PD28 and consisted of a single administration of ethanol (2.5 g/kg, i.g.) or its vehicle (0.0 g/kg, tap water). Then, during PD37–52, the adolescents were subjected to a procedure for the assessment of ethanol consumption, which consisted of four phases. The graph depicts ethanol intake during Phase 2. This phase lasted for 4 days, in which animals were given continuous, 24 h access to ethanol as the only fluid available in the homecage. Data in this figure are collapsed across ethanol treatment on PD31 (2.5 or 0.0 g/kg). This factor did not exert a significant main effect or significantly interact with the remaining variables. The vertical bars indicate SEM.

Figure 6

Left panel: Ethanol intake (g/kg) in female and male adolescent rats during Phase 2 of the intake protocol as a function of day of assessment (sessions 1, 2, 3, and 4) and sensitivity to ethanol treatment at initiation. Right panel: Mean intake of 6% ethanol (g/kg) in adolescent rats during phases 1 and 4 of the intake protocol as a function of sensitivity to ethanol treatment at initiation. Initiation occurred on PD28 and consisted of a single administration of ethanol (2.5 g/kg, i.g.) or its vehicle (0.0 g/kg, tap water). In these panels, ethanol-treated adolescents were divided into high- and low-responders by a split-median procedure that considered the total amount of forward locomotion evoked by ethanol during initiation on PD28. During PD37–52, the adolescents were subjected to a procedure for the assessment of ethanol consumption, which consisted of four phases. The graph in the left panel depicts ethanol intake during Phase 2. This phase lasted for 4 days, in which animals were given continuous, 24 h access to ethanol as the only fluid available in the homecage. The graph in the right panel depicts mean ethanol intake of 6% ethanol across Phases 1 and 4. During these phases adolescents were given daily two-bottle choice tests. On the first session, a 3% v/v ethanol solution was available together with the water. This solution was increased by 1% v/v of ethanol per day until reaching 6% v/v ethanol on session 4. Data in this figure are collapsed across ethanol treatment on PD31 (2.5 or 0.0 g/kg). The vertical bars indicate SEM.