Adolescent but not adult rats exhibit ethanol-mediated appetitive second-order conditioning

Background: Adolescent rats are less sensitive to the sedative effects of ethanol than older animals. They also seem to perceive the reinforcing properties of ethanol. However, unlike neonates or infants, ethanol‐mediated appetitive behavior is yet to be clearly shown in adolescents. Appetitive ethanol reinforcement was assessed in adolescent (postnatal day 33, P33) and adult rats (P71) through second‐order conditioning (SOC). Methods: On P32 or P70, animals were intragastrically administered ethanol (0.5 or 2.0 g/kg) paired with intra‐oral pulses of sucrose (CS₁, first‐order conditioning phase). CS₁ delivery took place either 5–20 (early pairing) or 30–45 minutes (late pairing) following ethanol administration. The time interval between CS₁ exposure and ethanol administration was 240 minutes in unpaired controls. On P33 or P71, animals were presented the CS₁ (second‐order conditioning phase) in a distinctive chamber (CS₂, second‐order conditioning). Then they were tested for CS₂ preference. Results: Early and late paired adolescents, but not adults, had greater preference for the CS₂ than controls, a result indicative of ontogenetic variation in ethanol‐mediated reinforcement. During the CS₁‐CS₂ associative phase, paired adolescents given 2.0 g/kg ethanol wall‐climbed more than controls. Blood and brain ethanol levels associated with the 0.5 and 2.0 g/kg doses at the onset of each conditioning phase did not differ substantially across age, with mean blood ethanol concentration of 38 and 112 mg%. Conclusions: These data indicate age‐related differences between adolescent and adult rats in terms of sensitivity to ethanol’s motivational effects. Adolescents exhibited high sensitivity for ethanol’s appetitive effects. These animals also showed ethanol‐mediated behavioral activation during the SOC phase. The SOC preparation provides a valuable conditioning model for assessing ethanol’s motivational effects across ontogeny.