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ABSTRACT: There is a scarcity of research on ethanol affinity in alcohol-preferring (P) rats before weaning and it is unknown if neonate P rats exhibit ethanol intake preferences comparable to those observed in adult P rats. This study examined ethanol intake in P and alcohol-nonpreferring (NP) rats 3 hr after birth (Experiment 1, surrogate nipple test), at postnatal days (PD) 8, 12, and 18 (Experiment 2, consumption from the floor procedure) and at adolescence (Experiment 3, two-bottle choice test at PD32). The high-preference genotype was readily expressed 3 hr after birth. P neonates drank twice as much ethanol as their NP counterparts. This heightened ethanol preference transiently reversed at P8, reemerged as weaning approached (P18) and was fully expressed during adolescence. These results help to clarify the ontogeny of genetic predisposition for ethanol. Genetic predisposition for higher ethanol intake in P than in NP rats seems to be present immediately following birth.
Developmental Psychobiology 04/2011; 53(3):234-45. · 2.98 Impact Factor
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ABSTRACT: It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age. Experiment 1 determined the parameters (i.e., dose, interval of conditioning) for assessing ethanol-mediated conditioning. Pups were then trained with differential Pavlovian conditioning (Experiments 2 and 3) in which ethanol intoxication (1.0-2.0 g/kg, intragastrically or intraperitoneally delivered) was paired with a tactile stimulus (sandpaper) while an alternative texture signaled the absence of ethanol's effects. Unpaired control conditions were also used. Tactile preferences were assessed after two conditioning sessions. Paired rats spent significantly more time on sandpaper than unpaired controls, an effect that was greater after intragastric administration of 1.0 than 2.0 g/kg ethanol. This effect was replicated in Experiments 4a and 4c and found to be inhibited by pretreatment with general (naloxone [NAL]) or specific (d-Pen-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 [CTOP] and naltrindole) opioid antagonists. Blood ethanol levels at conditioning were not altered by NAL (Experiment 4b). The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process.
Alcohol (Fayetteville, N.Y.) 09/2009; 43(5):347-58. · 2.41 Impact Factor
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ABSTRACT: Motivational effects of self-administered ethanol have rarely been studied in preweanling rats due primarily to the lack of age-appropriate operant tasks. The present experiments assessed the hedonic effects of intraoral ethanol in infant rats self-administered by activating a touch sensor. On postnatal day (PD) 13 pups were pre-exposed to the drug's pharmacological and/or sensory effects. Operant sessions were conducted during PDs 14-16 (Experiments 1 and 2). Paired animals were placed in chambers equipped with a touch-sensitive disk and received an intraoral infusion of ethanol (3 or 5% v/v, 5 microl) after each sensor contact. Yoked controls were equated for number and distribution of ethanol infusions but had no control over the contingency between operant behavior and intraoral infusion. In Experiment 2, training trials were preceded by a non-reinforced phase. Paired pups performed fewer operant responses than controls and decreased their operant responses across sessions. These results suggest that intraoral self-administered ethanol has an aversive hedonic value in two-week old rats. Operant behavior seems to have been associated with aversive orosensory effects derived from intraoral ethanol infusion.
Physiology & Behavior 02/2008; 93(1-2):118-29. · 2.87 Impact Factor
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ABSTRACT: While appetitive reinforcement effects of ethanol are easily detected in rat neonates, such phenomena rarely have been observed in older infants. Recently, Molina et al. [Molina, J. C., Ponce L. F., Truxell, E., & Spear N. E. (2006). Infantile sensitivity to ethanol's motivational effects: ethanol reinforcement during the third postnatal week. Alcohol Clin Exp Res 30, 1506-1519] reported such effects of ethanol in 14-day-olds using a second-order conditioning procedure. Infants also appear to be sensitive to biphasic reinforcement or general motivational effects of ethanol, with appetitive effects seeming to occur early in the state of intoxication and aversive effects predominant during late stages, but tests have been inconclusive. The present study examined the possibility of biphasic motivational effects of ethanol during infancy through the use of second-order conditioning procedures. Preweanling rats (14 days old) experienced intraoral water infusions (conditioned stimulus, CS) either 5-20 or 30-45 min after administration of 0.5 or 2.0 g/kg i.g. ethanol. Pups were then exposed to the CS while over a novel texture (second-order phase). Tests of tactile preference for that texture followed. Locomotive, thermal, hormonal (corticosterone release), and pharmacokinetic patterns likely to underlie the acquisition of ethanol-mediated conditioning were also examined in subsequent experiments. Intraoral CSs paired with either early or late effects of low-dose ethanol (0.5 g/kg, blood ethanol concentration: 40 mg%) became positive second-order reinforcers. Appetitive effects were also exhibited by pups exposed to the CS during commencement of the toxic episode induced by a 2.0 g/kg ethanol dose, 5-20 min after administration of ethanol, whereas aversions emerged when CS presentation occurred 30-45 min postadministration time (blood ethanol concentrations: 157 and 200 mg%, respectively). Overall, the results indicate that infants rapidly detect differential motivational properties of ethanol as a function of dose or drug postadministration time. Relatively neutral stimuli associated with these properties are later capable of acting as either positive or aversive reinforcers. Thermal and motor responses that accompany ethanol intoxication do not seem to be directly associated with differential hedonic properties of the drug at this stage of development.
Alcohol 02/2007; 41(1):41-55. · 2.47 Impact Factor
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ABSTRACT: 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.
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).
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%.
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.
Alcoholism Clinical and Experimental Research 10/2006; 30(9):1506-19. · 3.34 Impact Factor
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ABSTRACT: During the preweanling period, infant rats consume large quantities of ethanol without initiating procedures. Ethanol intake during this period has seemed to be age related, with peak consumption occurring near the end of the second postnatal week, on postnatal day (P)12, but only a narrow range of conditions has been tested.
Independent ingestion of ethanol was measured at each of two ages, P12 and P18, with systematic variation in ethanol concentration, duration of exposure, and mode of fluid presentation. Ethanol ingestion was measured in terms of percentage body weight gain, grams of absolute ethanol ingested per unit body weight, and blood ethanol concentration.
Ingestion of 30% ethanol during a 40-min period led to blood ethanol concentrations approaching 300 mg/100 ml at both P12 and P18. For ethanol concentrations of 10 or 20%, ingestion at P12 was greater than at P18. When ethanol was available from ethanol-soaked Kimwipe on the floor, ethanol intake transdermally or by inhalation was apparent but accounted for less than half of the overall ethanol intake. It was clear that for older infants, which are susceptible to ethanol's diuretic effects and are much more likely to self-void than those at P12, measurement of intake by percentage body weight gain can underestimate ethanol ingestion.
The infant rat ingests extraordinarily high levels of ethanol, in concentrations as high as 30%, without initiation procedures. Acceptance of ethanol by infants on first exposure contrasts with the conventional rejection of these concentrations by adults. It is unclear why younger infants (P12) consume more 10 and 20% ethanol than older (P18) infants. These and other differences in ethanol intake between infants and older animals may be due initially to the relative ontogeny of receptors for bitter and sweet taste and subsequently to other factors.
Alcoholism Clinical and Experimental Research 09/2004; 28(8):1200-11. · 3.34 Impact Factor
