Naloxone Blocks Ethanol-Mediated Appetitive Conditioning And Locomotor Activation In Adolescent Rats

PAUTASSI RM; NIZHNIKOV M; ACEVEDO MB; SPEAR NE

BEHAVIOURAL BRAIN RESEARCH

ELSEVIER SCIENCE BV

Año: 2011 vol. 216 p. 262 - 269

0166-4328

Age-related differences in ethanol sensitivity could put adolescents at risk for developing alcohol-related problems. Little information exists, however, about adolescent sensitivity to ethanol´s appetitive effects and the neurobiological mechanisms underlying ethanol reinforcement during this developmental stage. The present study assessed the role of the opioid system in adolescent rats in an appetitive second-order schedule of ethanol reinforcement and ethanol-induced locomotor stimulation. On postnatal day 32 (PD32), animals were pretreated with the general opioid antagonist naloxone (0.0, 0.75, 1.50, or 2.5 mg/kg) and then given pairings of ethanol (0.0 or 2.0 g/kg, intragastrically) with intraoral pulses of water (conditioned stimulus 1 [CS₁], first-order conditioning phase). CS₁ delivery occurred 30-45 min after ethanol administration when the effect of ethanol was assumed to be appetitive. On PD33, adolescents were exposed to CS₁ (second-order conditioning phase) while in a chamber featuring distinctive exteroceptive cues (CS₂). Preference for CS₂ was then tested. Adolescents given CS₁-ethanol pairings exhibited greater preference for CS₂ than controls, indicating ethanol-mediated reinforcement, but only when not pretreated with naloxone. Blood alcohol levels during conditioning were not altered by naloxone. Experiment 2 revealed that ethanol-induced locomotor activation soon after administration, and naloxone dose-dependently suppressed this stimulating effect. The present study indicates that adolescent rats are sensitive to ethanol´s reinforcing and locomotor-stimulating effects. Both effects of ethanol appear to be mediated by endogenous opioid system activation.