Ethanol-mediated operant learning in the infant rat leads to increased ethanol intake during adolescence.

Recent studies indicate that the infant rat has high affinity for ethanol ingestion and marked sensitivity to the drug's reinforcing effects [Spear, N.E., Molina, J.C. Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review. Alcohol Clin Exp Res 2005; 29: 909-29.]. A novel operant technique was developed to analyze reinforcing effects of ethanol delivery during the third postnatal week. The impact of this ethanol-reinforcement experience upon subsequent ethanol consumption during adolescence (postnatal weeks 5-6) was also examined. In Experiment 1, pups (postnatal days 14-17) were given an explicit contingency between nose-poking behavior and intraoral delivery of either water or 3.75% v/v ethanol (paired groups). Yoked controls (pups receiving either reinforcer independently of their behavior) were also included. Paired subjects reinforced with ethanol exhibited rapid and robust operant conditioning leading to blood ethanol concentrations in the 25-48 mg% range. In Experiment 2, a higher ethanol concentration (7.5% v/v) provided significant reinforcement. During adolescence, animals originally reinforced with 3.75% v/v ethanol exhibited greater ingestion of ethanol than control animals without prior ethanol reinforcement. These results indicate that, without extensive initiation to ethanol, infant rats rapidly learn to gain access to ethanol and that this experience has a significant impact upon later ethanol intake patterns.

Infantile sensitivity to ethanol's motivational effects: Ethanol reinforcement during the third postnatal week.

BACKGROUND: Although tests specific to newborn rats have frequently verified their susceptibility to the reinforcing properties of ethanol, demonstration of comparable reinforcing effects in older infants has been elusive. Using a second-order conditioning procedure, the present study assessed in preweanling rats whether pairing with early postabsorptive effects of ethanol would render intraorally delivered gustatory stimuli capable of positive reinforcement for association with a salient texture. Direct reinforcing effects of ethanol were also evaluated through intake tests of gustatory stimuli previously paired with the drug. Blood ethanol levels (BELs) were determined for each of the ethanol doses used. METHODS: Pups (14 days old) were stimulated with intraoral infusion of sucrose (10% v/v), water, or quinine (0.0045% w/v) 5 minutes after being intragastrically (i.g.) administered 0.00, 0.25, 0.50, or 2.00 g/kg ethanol (Experiments 1 and 2). These stimuli were then briefly presented while pups experienced a rough texture (sandpaper). Rats were subsequently evaluated in a 2-way texture location test (sandpaper vs smooth surface). In Experiment 3, sucrose, water, or quinine was paired with early postabsorptive effects of ethanol (0.00, 0.50, or 2.0 g/kg). Consumption of these stimuli was later assessed. Motor activity patterns during the intake test were also evaluated. In Experiment 4, BELs corresponding to 0.25, 0.50, or 2.0 g/kg ethanol were determined 5 and 20 minutes after i.g. administration (time periods were in accord with the onset and offset of intraoral stimulation used in the previous experiments). RESULTS: Intraoral infusion of sucrose, water, or quinine, while under a state of sobriety and paired with sandpaper, resulted in roughly 50% preference for this texture. Sandpaper preferences were significantly elevated in pups that had experienced sucrose or water in a nonsober state-while under the effects of ethanol (Experiments 1 and 2). This indicated reinforcing effects of the ethanol intoxication. Pairing ethanol intoxication directly with consumption of sucrose, water, or quinine did not affect their later consumption. Yet, there were clear indications that this pairing resulted in conditioned behavioral activity patterns. Blood ethanol levels corresponding to the ethanol doses used here ranged between 10 and 150 mg%. CONCLUSIONS: Infants appear sensitive to pharmacological reinforcing properties of low and relatively high ethanol doses. This sensitivity was revealed indirectly, by pairing gustatory stimuli with ethanol intoxication and then allowing these stimuli to act as second-order reinforcement for a quite different (tactile) stimulus. Behavioral activation elicited by the gustatory stimuli previously paired with a state of intoxication seems to compete with the expression of ethanol's motivational properties as assessed through intake tests.

Acute ethanol counteracts the acquisition of aversive olfactory learning in infant rats.

Rodents are particularly prone to acquire associative memories during early stages of life. Yet, very little is known about how ethanol interacts with simultaneous associative learning acquired during postabsorptive periods. We have recently observed that preweanling rats avoid lemon odor previously paired with the intraoral infusion of a sapid sweet solution, a result likely to be caused by aversive consequences inherent to this procedure. Two experiments were conducted to analyze the effects of acute ethanol upon the acquisition of this avoidance response. Fourteen-day-old Wistar rats were intragastrically administered with ethanol (0.0, 0.25, 0.5, or 1.25 g/kg) and then exposed for 5 min to a lemon-scented chamber while being intraorally infused with sucrose (12% vol/vol). Four of such pairings were conducted immediately after ethanol administration. Control pups experienced these stimuli in an unrelated fashion. On postnatal day 15 animals were tested in a 5-min, two-way odor-preference test. Pups administered with vehicle during the acquisition phase exhibited a strong aversion to the lemon odor relative to control subjects. This avoidance response was reduced in pups that received 0.5 and 1.25 g/kg doses, whereas it completely vanished in those that received 0.25 g/kg dose. In a second experiment it was observed that, 10 min after the administration, blood ethanol concentrations attained with the 0.25, 0.5, and 1.25 g/kg doses were 11, 39, and 83 mg%, respectively. These data indicate that a very low dose of ethanol is able to counteract early aversive associative learning, a result likely to be mediated by anxiolytic properties of ethanol.