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Prenatal alcohol exposure is associated with a variety of impairments in neonatal state regulatory systems. Since prenatal alcohol exposure causes thermoregulatory deficits in response to both heat and cold stress in rats, body temperature set-point might be altered in alcohol-exposed offspring. The effect of prenatal alcohol exposure on behavior in a thermocline was investigated in 10-, 15-, and 125-day-old male and female rats from three prenatal treatment conditions: alcohol liquid diet, pair-fed liquid diet control, or standard control. Subjects were placed in the thermocline in the cold, hot, or middle start positions and observed for 60 min. Subjects exposed to alcohol prenatally had a wider "preference zone" than control subjects at 10 and 15 days of age, but did not as adults. This widening of the temperature set-point in young subjects prenatally exposed to alcohol may represent a developmental lag in the development of body temperature set-point or a central compensatory process allowing the animal to adapt to alternating experiences of heat and cold stress.

Prenatal alcohol exposure is associated with a variety of impairments in neonatal state regulatory systems. Since prenatal alcohol exposure causes thermoregulatory deficits in response to both heat and cold stress in rats, body temperature set-point might be altered in alcohol-exposed offspring. The effect of prenatal alcohol exposure on behavior in a thermocline was investigated in 10-, 15-, and 125-day-old male and female rats from three prenatal treatment conditions: alcohol liquid diet, pair-fed liquid diet control, or standard control. Subjects were placed in the thermocline in the cold, hot, or middle start positions and observed for 60 min. Subjects exposed to alcohol prenatally had a wider "preference zone" than control subjects at 10 and 15 days of age, but did not as adults. This widening of the temperature set-point in young subjects prenatally exposed to alcohol may represent a developmental lag in the development of body temperature set-point or a central compensatory process allowing the animal to adapt to alternating experiences of heat and cold stress.

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction. However, it remains unclear whether ethanol-paired CS increase ethanol-choice that is not in extinction. Here, we examine the effects of an ethanol-paired CS on ethanol-choice when both food- and ethanol-responding are reinforced. Sixteen adult male Lewis rats were trained on a concurrent schedule to respond for ethanol on one lever and for food on the other lever. Ethanol was available under an FR 5 schedule, and food was available under an FR schedule that was adjusted for each rat to earn an equal number of food and ethanol deliveries. Then, 2-min light presentations were paired with an RT 25-sec schedule of ethanol delivery for 10 sessions in the absence of both levers. After this, subjects were placed back on the concurrent schedule for one session, then five sessions with the CS being present or absent on each trial of the concurrent schedule occurred. Rats learned to respond on one lever for ethanol and on the other for food and earned similar numbers of ethanol and food deliveries. During Pavlovian Conditioning, the number of head entries into the head-entry detector was higher in the presence of the CS than in its absence. In the test sessions, rats made more ethanol responses in the presence of the CS than in its absence. However, this effect was small and did not increase the amount of ethanol earned. Thus, ethanol-paired CS could increase ethanol-responding under a choice procedure but did not increase ethanol consumption meaningfully under the studied conditions.

The influence of Pavlovian Conditioned Stimuli (CS) on ethanol self-administration and choice between ethanol and an alternative are potentially important. Ethanol-paired CS might increase ethanol self-administration, especially when it has been reduced during recovery, though the selectivity of these increases has been questioned. To date, one study examined the effects of an ethanol-paired CS on ethanol choice and found that the CS increased ethanol-responding more than food-responding when both were in extinction. However, it remains unclear whether ethanol-paired CS increase ethanol-choice that is not in extinction. Here, we examine the effects of an ethanol-paired CS on ethanol-choice when both food- and ethanol-responding are reinforced. Sixteen adult male Lewis rats were trained on a concurrent schedule to respond for ethanol on one lever and for food on the other lever. Ethanol was available under an FR 5 schedule, and food was available under an FR schedule that was adjusted for each rat to earn an equal number of food and ethanol deliveries. Then, 2-min light presentations were paired with an RT 25-sec schedule of ethanol delivery for 10 sessions in the absence of both levers. After this, subjects were placed back on the concurrent schedule for one session, then five sessions with the CS being present or absent on each trial of the concurrent schedule occurred. Rats learned to respond on one lever for ethanol and on the other for food and earned similar numbers of ethanol and food deliveries. During Pavlovian Conditioning, the number of head entries into the head-entry detector was higher in the presence of the CS than in its absence. In the test sessions, rats made more ethanol responses in the presence of the CS than in its absence. However, this effect was small and did not increase the amount of ethanol earned. Thus, ethanol-paired CS could increase ethanol-responding under a choice procedure but did not increase ethanol consumption meaningfully under the studied conditions.

The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia.

The effects of the GABAA receptor antagonists, pentylenetetrazol, bicuculline, and picrotoxin, the glycine antagonist, strychnine, and the NMDA receptor antagonist, memantine, on ethanol-induced behavioral sleep and body temperature were investigated. Pentylenetetrazol, bicuculline, and picrotoxin given prior and following ethanol reduced the behavioral sleep and potentiated the hypothermia caused by ethanol. However, convulsions appeared when bicuculline, but not pentylenetetrazol and picrotoxin, were given following ethanol. After the reversal of unconsciousness in rats without convulsions the animals remained awake throughout the experiments without motor incoordination, hyperexcitability, and sedation, but they were in hypothermia within 12 h. The glycine antagonist, strychnine, given prior or after ethanol had virtually no effect on ethanol-induced behavioral sleep and hypothermia. Ethanol given prior or following strychnine failed to antagonize strychnine-induced convulsions. The NMDA receptor antagonist, memantine, given following ethanol potentiated the behavioral sleep and had virtually no effect on hypothermia induced by ethanol. It is suggested that the ethanol-induced behavioral sleep may be attributed to its ability to enhance the GABAergic mechanisms and to inhibit NMDA-mediated excitatory responses. However, the ethanol-induced hypothermia may be ascribed solely to the facilitation of GABAergic transmission. Further, it is postulated that a bidirectional inhibitory system subserves the regulation of behavioral sleep and convulsions. However, one-way inhibitory system underlies the ethanol-induced hypothermia.

Atp1a2 has been previously studied for anxiety, learning and motor function disorders, and fear. Since Atp1a2 has been shown to be involved in anxiety and this behavior is a known risk factor for developing alcoholism, we have been investigating Atp1a2 for its potential role in responses to alcohol. This study utilized Atp1a2 knockout mice; Atp1a2 heterozygous mice, with half the amount of protein compared to wild-type mice, were used because Atp1a2 homozygous null mice die shortly after birth. The alcohol-related behavioral experiments performed were loss of righting reflex (LORR), acute alcohol withdrawal measured by handling-induced convulsions (HIC), drinking in the dark (DID), open-field activity (OFA), and elevated plus-maze (EPM). LORR was a 2-day test that measures acute alcohol sensitivity, and rapid and acute functional tolerance (AFT). HIC was a 3-day test to measure alcohol withdrawal, DID was a 4-day test which measures voluntary alcohol consumption, and OFA and EPM measured anxiety with alcohol exposure. The effect of genotype on alcohol metabolism was also examined. There was a genotype effect on rate of alcohol metabolism, but only in males. There was no effect on alcohol withdrawal severity. The Atp1a2 heterozygous mice consumed more alcohol than wild-type mice in the DID test, although only in males. In addition, only males were observed to show rapid tolerance in the LORR test while only female heterozygous mice showed a pretreatment effect on AFT. Alcohol exposure had a greater anxiolytic effect in the heterozygous mice compared to wild-type mice, although, again, there were sex effects with only males showing the effect in OFA and only females in the EPM. Although the behavioral results were mixed, there does appear to be a connection between anxiety and alcohol. Overall, the results suggest that Atp1a2 does contribute to alcohol-related behaviors, although the effect is modest with a clear dependence on sex.

Atp1a2 has been previously studied for anxiety, learning and motor function disorders, and fear. Since Atp1a2 has been shown to be involved in anxiety and this behavior is a known risk factor for developing alcoholism, we have been investigating Atp1a2 for its potential role in responses to alcohol. This study utilized Atp1a2 knockout mice; Atp1a2 heterozygous mice, with half the amount of protein compared to wild-type mice, were used because Atp1a2 homozygous null mice die shortly after birth. The alcohol-related behavioral experiments performed were loss of righting reflex (LORR), acute alcohol withdrawal measured by handling-induced convulsions (HIC), drinking in the dark (DID), open-field activity (OFA), and elevated plus-maze (EPM). LORR was a 2-day test that measures acute alcohol sensitivity, and rapid and acute functional tolerance (AFT). HIC was a 3-day test to measure alcohol withdrawal, DID was a 4-day test which measures voluntary alcohol consumption, and OFA and EPM measured anxiety with alcohol exposure. The effect of genotype on alcohol metabolism was also examined. There was a genotype effect on rate of alcohol metabolism, but only in males. There was no effect on alcohol withdrawal severity. The Atp1a2 heterozygous mice consumed more alcohol than wild-type mice in the DID test, although only in males. In addition, only males were observed to show rapid tolerance in the LORR test while only female heterozygous mice showed a pretreatment effect on AFT. Alcohol exposure had a greater anxiolytic effect in the heterozygous mice compared to wild-type mice, although, again, there were sex effects with only males showing the effect in OFA and only females in the EPM. Although the behavioral results were mixed, there does appear to be a connection between anxiety and alcohol. Overall, the results suggest that Atp1a2 does contribute to alcohol-related behaviors, although the effect is modest with a clear dependence on sex.

Craniofacial bone dysmorphology is an important but under-explored potential diagnostic feature of fetal alcohol spectrum disorders. This study used longitudinal MicroCT 3D imaging to examine the effect of prenatal alcohol exposure on craniofacial bone growth in a mouse model. C57BL/6J dams were divided into 3 groups: alcohol 4.2% v/v in PMI® liquid diet (ALC), 2 weeks prior to and during pregnancy from embryonic (E) days 7-E16; pair-fed controls (PF), isocalorically matched to the ALC group; chow controls (CHOW), given ad libitum chow and water. The MicroCT scans were performed on pups on postnatal days 7 (P7) and P21. The volumes of the neurocranium (volume encased by the frontal, parietal, and occipital bones) and the viscerocranium (volume encased by the mandible and nasal bone), along with total skull bone volume, head size, and head circumference were evaluated using general linear models and discriminant analyses. The pups in the alcohol-treated group, when compared to the chow-fed controls (ALC vs CHOW) and the isocaloric-fed controls (ALC vs PF), showed differences in head size and circumference at P7 and P21, the total skull volume and parietal bone volume at P7, and volume of all the tested bones except nasal at P21. There was a growth trend of ALC CHOW), and the total skull, parietal bone, and occipital bone at P21 (ALC < CHOW, ALC < PF). While covarying for the P7 measures, the treatment affected only the 3 neurocranial bones at P21 (ALC < CHOW, ALC < PF). Discriminant analysis sensitively selected between ALC and CHOW (AUC = 0.967), between ALC and PF (AUC = 0.995), and between PF and CHOW (AUC = 0.805). These results supported our hypothesis that craniofacial bones might be a reliable and sensitive indicator for the diagnosis of prenatal alcohol exposure. Significantly, we found that the neurocranium (upper skull) was more sensitive to alcohol than the viscerocranium (face).