Neurophysiological profiles of replicate line 2 high-alcohol-drinking (HAD-2) and low-alcohol-drinking (LAD-2) rats.

RATIONALE: A select number of electrophysiological findings have been demonstrated to differentiate rat lines selectively bred for high and low ethanol preference. OBJECTIVE: In the present study, EEGs and event-related potentials (ERPs) of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats from replicate line 2 (HAD-2 and LAD-2) were assessed to determine if their neurophysiological profiles are similar to selected lines previously evaluated. METHODS: Rats obtained from Indiana University were implanted with cortical and amygdalar recording electrodes. Baseline EEG and ERPs were assessed in ethanol-naïve HAD-2 and LAD-2 rats. Animals subsequently were trained to self-administer ethanol by using a sucrose-substitution procedure. RESULTS: Compared with LAD-2 rats, HAD-2 rats displayed greater parietal cortical power in the 6 to 32 Hz frequency range of the EEG. Greater parietal cortical peak frequency in the 2 to 4 Hz range and decreased frontal, parietal, and amygdalar peak frequencies in the 16 to 32 Hz frequency range were also seen. Compared with LAD-2 rats, HAD-2 rats had decreased P2 latency of ERPs recorded in the parietal cortex. HAD-2 rats also had greater frontal, parietal, and amygdalar P2 amplitudes, greater frontal and parietal cortical P1 amplitudes, and greater parietal cortical P3 amplitudes compared with LAD-2 rats. As anticipated, HAD-2 rats consumed significantly greater levels of sucrose, sucrose-ethanol, and ethanol over the course of the sucrose-substitution procedure compared with LAD-2 rats. CONCLUSIONS: These data suggest that increased cortical power is associated with high ethanol preference in a number of selectively bred rat lines. However, unique electrophysiological characteristics may index alcohol preference in each line.

Neuropeptide Y administration into the third ventricle does not increase sucrose or ethanol self-administration but does affect the cortical EEG and increases food intake.

RATIONALE: Several studies have provided indirect evidence that neuropeptide Y (NPY) may play a role in the regulation of ethanol consumption. However, the direct effects of central NPY administration on ethanol drinking are unclear. OBJECTIVE: This study examined the effects of NPY on ethanol, sucrose, and food consumption as well as its concomitant effects on the cortical EEG. METHODS: Wistar rats were implanted with cortical recording electrodes and a cannula in the third ventricle after using a sucrose substitution procedure to establish ethanol self-administration. NPY (0-15 microg/3.0 microl) was infused into the third ventricle prior to drinking sessions, when 10% ethanol (10E), 2% sucrose (2S), 0.5% sucrose (0.5S), or food were available. Behavior and cortical EEG were monitored during the sessions. RESULTS: NPY had no effect on the intake of 10E, 2S, or 0.5S, but NPY (15 microg/3.0 microl) significantly increased food intake. Under baseline drinking conditions, EEG power in the 6-8 Hz range was significantly greater when 2S was consumed compared to 10E. NPY decreased power in the 8-16 Hz range, decreased peak frequency in the 6-8 Hz range, and increased peak frequency in the 32-50 Hz range when 10E or 2S was available. CONCLUSIONS: These data suggest that NPY administration into the third ventricle preferentially regulates feeding compared to ethanol or sucrose drinking. In addition, since NPY significantly altered the cortical EEG in the absence of effects on ethanol and sucrose consumption, these data may indicate that NPY's cortical EEG effects are more related to its sedative or anxiolytic properties, rather than any effect on consumption.

Periadolescent alcohol exposure has lasting effects on adult neurophysiological function in rats.

Most individuals have their first experience with ethanol (EtOH) consumption as adolescents. Episodes of high EtOH drinking, lasting from hours to days (i.e. binges), are not uncommon. Thus, adolescent EtOH drinking has become a significant health concern due to the possible protracted effects of high doses of EtOH on behavior and the developing brain. This study assessed the effects of brief high levels of EtOH during periadolescence on subsequent behavior and electrophysiology in adult rats. Male Sprague-Dawley rats were exposed to EtOH vapor for 5 days (i.e. postnatal days 35-40) or 10 days (i.e. postnatal days 30-40) for 12 h/day. Locomotor activity, EEG activity, and event-related potentials (ERPs) were then assessed at 1 and 6-7 weeks post EtOH exposure. Significant differences in locomotor activity were not observed at 1 week or 6-7 weeks post-ethanol exposure. However, EtOH exposure did have long-term electrophysiological effects. EtOH exposure increased the frequency of the EEG in the 1-2 Hz range in the parietal cortex and the 16-32 Hz range in the hippocampus. EtOH exposure also increased hippocampal N2 amplitude, decreased hippocampal P3 amplitude, and decreased cortical and hippocampal P2 amplitudes. While these findings are generally similar to those reported following long-term ethanol exposure during adulthood, alcohol exposure during adolescence appears to produce more robust hippocampal effects following shorter periods of exposure. In addition, these data indicate that, in the absence of overt behavioral differences, there are long-lasting changes in the functional brain activity of adult rats briefly exposed to high levels of EtOH during the periadolescent period.

Approaches to understanding the neurobiological regulation of ethanol self-administration: a young investigators forum.

The article represents the proceedings of a symposium at the 2000 RSA Meeting in Denver, Colorado. The co-chairs were Cristine L. Czachowski and Craig J. Slawecki. The presentations were (1) Behavioral assessment of ethanol seeking and self-administration, by Cristine L. Czachowski; (2) Electrophysiological measures of ethanol preference and reinforcing efficacy, by Craig J. Slawecki; (3) Genetic differences in locomotor sensitization and reward phenotypes associated with bidirectional selection for alcohol preference in mice, by Nicholas J. Grahame; (4) Transgenic and knockout mouse models: Powerful tools for investigating the neurobiology of alcoholism, by Todd E. Thiele; and (5) Neurochemical characteristics that may predict ethanol preference in selected P and NP rats: A quantitative microdialysis study, by Simon N. Katner.

Substance P and neurokinin levels are decreased in the cortex and hypothalamus of alcohol-preferring (P) rats.

OBJECTIVE: Central tachykinin levels (i.e., substance P [SP], neurokinin A [NKA], neurokinin B [NKB] and neurokinin K [NKK]) have been reported to fluctuate in association with stress and anxiety. Ethanol can also modulate stress and anxiety. Further, ethanol intake can change as a result of stress and anxiety. This suggests possible interactions between ethanol and central tachykinins, i.e., changing tachykinin levels could influence ethanol intake and vice versa. However, to date few studies have assessed the potential relationship between tachykinin levels in the brain and ethanol preference. The present study was designed to determine if rodent lines selectively bred for differences in alcohol preference (i.e., alcohol-preferring [P] and non-preferring [NP] rats) have different tachykinin levels in the brain. METHOD: Tissue samples from the brains of ethanol-naive P and NP rats were collected from the frontal cortex, caudate, hippocampus, amygdala and hypothalamus. Using radioimmuno assays, concentrations of SP-like immunoreactivity (SP-LI) and neurokinin-like immunoreactivity (NK-LI, i.e., neurokinin A, B and K) in P and NP rats were determined. RESULTS: In P rats, SP-LI was significantly lower in the frontal cortex (F= 12.80, 1/26 df, p = .001) while NK-LI was significantly lower in the frontal cortex (F = 7.36, 1/26 df, p = .012) and hypothalamus (F = 5.32, 1/26 df, p = .029) compared with NP rats. CONCLUSIONS: These data indicate that endogenous SP and neurokinin levels are reduced in discrete brain regions of P rats compared with NP rats. These decreases may be associated with decreased serotonergic innervation of these brain regions in P rats compared with NP rats.

Nicotine exposure during the neonatal brain growth spurt produces hyperactivity in preweanling rats.

Despite warning labels and increases in evidence of the adverse effects of tobacco use, women continue to use tobacco products during pregnancy. Cigarette smoking has been linked to increased prenatal mortality, increased incidence of SIDS, reductions in birth weight, and disruptions in CNS and behavioral development. Animal model systems have critically established the causal relationship between nicotine and adverse developmental outcome. The present study examines the behavioral effects of nicotine exposure in the rat during the third trimester equivalent of the human brain growth spurt, a period of rapid development of the cholinergic systems and a period during which the CNS is particularly vulnerable to a number of insults. Sprague-Dawley rat pups were exposed to nicotine (6.0 mg/kg/day) from postnatal days (PD) 4-9 via an artificial rearing procedure. This procedure ensures that observed effects are not due to nutritional deficits. Two control groups were employed, an artificially reared control group and a normally reared control group. Activity level was measured on PD 18-19. Nicotine-exposed subjects were significantly overactive compared to both control groups, which did not differ significantly from one another. This behavioral alteration was observed in the absence of nicotine-induced body weight deficits. These results suggest that women who use tobacco products during late gestation may place their fetuses at risk for hyperactivity later in life, particularly during early adolescence.

Neurophysiological findings and drinking levels in high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats.

BACKGROUND: Specific neurophysiological profiles, such as reduced P300 amplitude or altered spectral power in the EEG, have been associated with a risk for alcoholism in several clinical populations. In certain rodent models, high versus low alcohol consumption is associated with similar neurophysiological differences. For example, alcohol-preferring (P) rats have increased spectral power and decreased P300 amplitudes compared with alcohol-nonpreferring (NP) rats. In the present study, the neurophysiological profiles of high-alcohol-drinking (HAD) and low-alcohol-drinking (LAD) rats were assessed (1) to determine if their electrophysiological profiles are similar to P and NP rats and (2) to examine the relationship of these neurophysiological indices to ethanol drinking. METHODS: Ethanol-naive HAD and LAD rats were implanted with cortical and amygdalar recording electrodes. Baseline EEG and event-related potentials (ERPs) then were assessed. Subsequently, all rats were trained to self-administer ethanol by using a sucrose-substitution procedure. RESULTS: Baseline EEG and ERP (i.e., pre-ethanol exposure) were assessed based on line (HAD versus LAD) and actual ethanol consumption (high drinkers versus low drinkers). At baseline, ethanol-naive HAD rats displayed significantly greater power in the cortical EEG and decreased amygdala N1 ERP amplitude compared with ethanol-naive LAD rats. Similar EEG and ERP profiles have been observed when P and NP rats are compared. No differences in P300 between lines were observed, but high-drinking rats, independent of line, had significantly decreased P300 amplitude in the amygdala compared with low-drinking rats. CONCLUSIONS: These data suggest there are some similarities in EEG and ERP profiles of P and HAD rats compared with NP and LAD rats. Furthermore, the data suggest that decreased P300 amplitude in the amygdala is associated with increased limited access ethanol drinking.

Effects of allopregnanolone on the EEG of alcohol-preferring and alcohol-nonpreferring rats.

BACKGROUND: Alcohol preferring (P) and alcohol-nonpreferring (NP) rats have been shown to have differing behavioral and electrophysiological responses to drugs that are positive modulators of the gamma-aminobutyric acid type A (GABA-A) receptor complex, such as ethanol and benzodiazepines. The neuroactive steroid allopregnanolone is also a positive modulator of GABA-A receptors; therefore, we hypothesized that P and NP rats would respond differently to intraperitoneally administered allopregnanolone. METHODS: Male P and NP rats were implanted with screw electrodes that overlay the frontal and parietal cortices and with a depth electrode aimed at the amygdala. Allopregnanolone (0.0-10.0 mg/kg ip) was administered 10 min before recording the EEG. RESULTS: Allopregnanolone increased high-frequency power (8-32 Hz) in the cortex and amygdala of both P rats and NP rats. In addition, allopregnanolone increased the predominant frequency of the cortical EEG in the 8 to 16 Hz bandwidth, decreased the predominant frequency in the 32 to 50 Hz bandwidth, and increased EEG variability (16-50 Hz). The effects of allopregnanolone were qualitatively similar in P and NP rats. However, P rats were more sensitive to low doses of allopregnanolone in cortex, whereas NP rats responded to lower doses of allopregnanolone in the amygdala. CONCLUSIONS: These data indicate that P and NP rats differ in their sensitivity to the EEG effects of allopregnanolone in the cortex and amygdala, which suggests that differences in GABAergic systems between P and NP rats may contribute to some of the differences observed in their behavioral repertoire.

Increases in sucrose consumption, but not ethanol consumption, following ICV NPY administration.

Neuropeptide Y (NPY) is a centrally acting neuromodulator that influences both consummatory behaviors and anxiety. NPY's effects on feeding are primarily regulated through Y5 receptors in hypothalamic sites, whereas NPY-induced anxiolysis appears to be mediated by Y1 receptors in the amygdala. Recently, NPY has been postulated to play a role in the regulation of ethanol consumption. The present study assessed the influence of intracerebroventricular (ICV) administration of NPY on the consumption of 10% ethanol or 2% sucrose in rats. Male Wistar rats were trained to self-administer 10% ethanol using the sucrose-substitution procedure and then implanted with an intracerebroventricular (ICV) cannula. The effects of NPY (0-15 microg) on ethanol consumption and sucrose consumption were then examined. ICV NPY infusion had no significant effects on the consumption of 10% ethanol, however, NPY significantly increased the consumption of 2% sucrose, [F(1, 11) = 6.18, p = 0.03]. These data suggest that ethanol intake and sucrose intake are differentially regulated by NPY. It is hypothesized that ICV infusion of NPY may be affecting both Y1 and Y5 receptors producing increased consummatory drive and anxiolysis, two factors that have opposing effects on subsequent ethanol consumption. Therefore, additional studies including site specific injection of NPY will be necessary to provide further insight into the role of NPY on ethanol consumption.

A new assessment of the ability of oral ethanol to function as a reinforcing stimulus.

BACKGROUND: In animal studies, the ability of ethanol to function as a reinforcer has been described as weak to moderate. This is in contrast with the human condition, where the consumption of alcoholic beverages can result in a variety of unwanted drinking behaviors. However, when the ethanol self-administration pattern is examined, animal studies over the last several years indicate that the ability of ethanol presentation to maintain behavior may be greater than originally assumed. METHODS: We reevaluated the ability of ethanol to function as a reinforcing stimulus in two paradigms by using an analysis of drinking bout characteristics. Data from previous studies that employed two self-administration models were analyzed. With the "dipper" model, small amounts of ethanol are presented after each completion of a response requirement; with the "sipper" model, the animal is allowed access to a drinking tube that contains ethanol for an extended period after completing a single response requirement. For both models, the consumption pattern could be characterized as occurring in a bout. Each drinking bout was divided into runs within the bout, and run rates and size were analyzed. As well, in the sipper model, the data on response requirement size were reviewed to demonstrate the ability of ethanol presentation to maintain high levels of responding in this model. RESULTS: From this assessment, we suggest that ethanol presentation in non-food- or non-water-restricted rats is as reinforcing as many other stimuli generally considered to be strong reinforcers (i.e., food in food-restricted rats). Using run size, we demonstrated that intake control appears to be regulated by shifts in run size during the bout and not run rate. CONCLUSIONS: Assessment of the pattern of ethanol consummatory bouts and the behaviors that precede them is critical in understanding how ethanol functions as a reinforcer. By using a drinking pattern analysis, the shifts in the momentary salience of the ethanol stimulus can be evaluated in these animal models. In addition, the separation of responding required to gain access to ethanol from consumption of ethanol demonstrated that ethanol presentation in this procedure can be a strong reinforcer for rats.

Comparison of the neurophysiological effects of allopregnanolone and ethanol in rats.

RATIONALE: The central nervous system actions of allopregnanolone (3 alpha-hydroxy-5 alpha-pregnan-20-one) and ethanol are at least partially mediated by modulation of gamma-aminobutyric acid (GABA)-A receptors. Although ethanol and allopregnanolone have similar behavioral effects, their macro-electrophysiological profiles have not been directly compared. OBJECTIVE: The purpose of this study was to compare the effects of allopregnanolone and ethanol on the electroencephalogram (EEG) and event-related potentials (ERPs). METHODS: Male Wistar rats were implanted with cortical and amygdalar electrodes. The rats were then administered allopregnanolone (0.0-10 mg/kg), ethanol (0.0-1.0 g/kg), or a combination of the two before recording. RESULTS: Allopregnanolone and ethanol had similar effects on ERPs. When administered alone, both decreased cortical P1-N1 ERP amplitude by 25-50% and N1 amplitude in the amygdala by 75-80%. Combined administration of ethanol (0.50 g/kg) and allopregnanolone (5.0 mg/kg), doses which were ineffective alone, decreased N1 amplitude in the amygdala by 60%. Allopregnanolone and ethanol had dissimilar EEG effects. Allopregnanolone increased high frequency power in the cortex and amygdala by 25-30%. Ethanol decreased cortical and amygdalar power in the same high frequency bands by 25-45%. Allopregnanolone, but not ethanol, also shifted cortical frequency in the 32- to 50-Hz band. Combined administration of allopregnanolone and ethanol had no effect on EEG power but enhanced allopregnanolone's effect on cortical frequency. CONCLUSIONS: These data suggest that allopregnanolone's macro-electrophysiological profile resembles barbiturates and benzodiazepines more than ethanol. Further, the interactions of allopregnanolone and ethanol appear complex, with multiple effects observed (enhancement or reversal) depending on the neurophysiological variable assessed.

Neonatal nicotine exposure alters hippocampal EEG and event-related potentials (ERPs) in rats.

A consensus is forming that nicotine can damage the developing rat central nervous system. However, few studies have assessed the electrophysiological effects of neonatal nicotine exposure in rodents in brain regions known to be sensitive to the teratogenic properties of nicotine. In a previous study it was reported that 1.0 and 4.0 mg/kg/day nicotine exposure from postnatal days 4-9, a developmental period corresponding to human third-trimester exposure, significantly altered hippocampal event-related potentials (ERPs) but did not effect cortical ERPs, cortical EEG, or hippocampal EEG. Because alterations in behavior and cortical/hippocampal neurochemistry and morphology have been reported following nicotine exposure, the present study used a higher dose of nicotine during the postnatal period (6.0 mg/kg/day) determine if functional changes in the EEG of these regions might contribute to behavioral changes that have been observed. Male Sprague-Dawley rats were exposed to 6. 0 mg/kg/day nicotine via gastric infusion using an artificial rearing, "pup-in-the-cup," technique for 6 consecutive days (postnatal days 4-9). At adulthood, EEG and auditory ERPs were recorded from the cortex and hippocampus. There were no significant differences in EEG or ERPs recorded from the cortex between nicotine-treated and control subjects. Examination of the hippocampal EEG revealed significantly decreased power in the 1-2-Hz frequency band of nicotine-treated rats. In addition, there was a significantly attenuated P300 ERP response to a noise tone in the nicotine-treated rats compared to controls. These data indicate that neonatal nicotine exposure alters functional activity in the hippocampus of adult rats. These effects are likely to be the result of synaptic disorganization in the hippocampus, and indicate that neonatal nicotine exposure exerts teratogenic effects on the developing central nervous system, particularly the hippocampus, which persist into adulthood.

Effects of chronic ethanol exposure on sleep in rats.

Sleep disturbance is a common complaint in alcoholics. When polysomnographic studies are performed in alcoholics, reductions in slow wave sleep are a common finding; however, few studies have evaluated the effects of chronic alcohol exposure on sleep in animal models. In the present study, the sleep EEG was evaluated in 40 Wistar rats who were exposed to chronic alcohol or control conditions in vapor chambers. Rats were exposed to ethanol vapors or control chambers for 6 weeks and then withdrawn. Sleep EEG was recorded before exposure (baseline), immediately following exposure, and 5 weeks after withdrawal from the ethanol/control chambers. In the ethanol-exposed animals, blood ethanol levels averaged 192 mg/dL over 6 weeks of exposure. Chronic ethanol exposure and withdrawal was not found to affect either slow wave sleep latency or slow wave sleep duration; however, overall spectral power as well as power in the delta, theta, and beta frequencies were significantly reduced following chronic exposure (2-4 Hz, [F(1, 17) = 18.11, p = 0.001], 4-6 Hz, [F(1, 17) = 15.98, p = 0.001], 6-8 Hz [F(1, 17) = 15.52, p = 0.001], 8-16 Hz band [F(1, 17) = 18.73, p < 0.0001], 16-32 Hz [F(1, 17) = 10.13, p = 0.005], and 1-50 Hz [F(1, 17) = 17.03, p = 0.001]. After 5 weeks of withdrawal, significant decreases still persisted in the delta and theta frequencies (2-4 Hz [F(1, 16) = 6.21, 0.024], 4-6 Hz [F(1, 16) = 6.26, 0.024], and 6-8 Hz [F(1, 16) = 4.84, p = 0.043]). These findings suggest that spectral analysis of the EEG is a highly sensitive measure of the effects of ethanol on sleep. These findings additionally demonstrate that chronic ethanol exposure can produce persistent diminution in the systems that generate cortical slow waves in the rat and thus may provide a model for understanding the mechanisms underlying sleep disturbances associated with alcoholism.

Effects of prolonged ethanol exposure on neurophysiological measures during an associative learning paradigm.

Long-term ethanol exposure has been reported to produce electrophysiological and cognitive impairments in some alcoholics. This study assessed the effects of chronic ethanol exposure on neurophysiological indices of associative learning in rats. Male Wistar rats (46) were exposed to ethanol vapor (EtOH group) or air (control group) for 6 consecutive weeks. After the animals were withdrawn from ethanol, electrodes were implanted in the frontal and parietal cortices and in the amygdala. Following a prolonged abstinence from ethanol (10-15 weeks), rats were exposed to a classical conditioning paradigm in which a food pellet was paired with the presentation of an auditory stimulus. During the first five sessions (conditioning phase), food pellet presentation was paired with the presentation of an infrequently presented tone. During the second five sessions (extinction phase), the association between food pellet presentation and the infrequently presented tone was weakened by no longer presenting food pellets following the infrequent tone. During selected test sessions, event-related brain potentials (ERPs) elicited by each tone (i.e. food-paired tone, non-paired tone) were recorded and analyzed. These analyses revealed differences in ERP responses between the groups. The latency of the N1 and P2 ERP components in the cortex of the control group, but not the EtOH group, increased during sessions when the association between food pellet delivery and tone presentation was being established or extinguished. These data support the hypothesis that chronic ethanol treatment results in a loss of responsivity in ERP components sensitive to changes in food-tone associations, even following a prolonged period of withdrawal from ethanol.

Neurophysiological effects of intracerebroventricular administration of urocortin.

The recently isolated Corticotropin Releasing Factor (CRF) related peptide, urocortin, has been reported to elicit a different behavioral profile than that of CRF. CRF is a potent anxiogenic agent and stimulant of motor activity whereas under similar conditions urocortin is a potent anorectic and mild locomotor stimulant. The neurophysiological effects of this newly synthesized peptide have not yet been examined. The present study evaluated the effects of intracerebroventricular administration of 3 doses of urocortin on the electroencephalogram (EEG) and on Event-Related Potentials (ERPs) in rats. Twenty male Wistar rats were implanted with electrodes in the amygdala and dorsal hippocampus, a cannula into the lateral ventricle, and skull surface electrodes over the frontal and parietal cortices. Following recovery from surgery, urocortin (0.01-1.0 microg) was infused into the lateral ventricle 5 min prior to the recording of EEG (10 min) and ERPs (10 min). Urocortin at any of the doses, did not produce any electrographic or behavioral signs of seizure activity. The predominant effect of urocortin infusion on EEG spectral activity was an increase in mean power in the 4-16 Hz range in the frontal cortex and a decrease in EEG stability in the frontal cortex and amygdala. Urocortin administration also decreased the latency of the P3 component of the ERP in the amygdala and hippocampus. These neurophysiological effects, that only partially overlap with those of CRF, are consistent with the behavioral profile described following urocortin administration in rats. Overall, these data further support the assertion that urocortin functions as a mild CNS stimulant enhancing arousal, as measured by EEG, and modulating the speed of stimulus evaluation as measured by ERPs.

Effects of chronic ethanol exposure on neurophysiological responses to corticotropin-releasing factor and neuropeptide Y.

Stress has been reported to influence ethanol consumption and relapse in abstinent alcoholics. The present study examined if prolonged alterations in neurophysiological responses to corticotropin-releasing factor (CRF) and neuropeptide Y (NPY), peptides known to influence stress responses, would persist during protracted ethanol abstinence. Male Wistar rats were chronically exposed to ethanol vapour (EtOH group) or air (control group) for 6 weeks. Upon removal from the vapour chambers, recording electrodes were implanted in the cortex and amygdala. The effects of intracerebroventricular infusions of CRF and NPY on electroencephalogram (EEG) and event-related potentials (ERPs) were then assessed 10-15 weeks after withdrawal from ethanol. Following abstinence from ethanol, the EtOH group displayed increased power in the 6-8 Hz frequency range and increased stability in the cortical EEG. In addition, in the EtOH group the amplitude of the P2 ERP component in the frontal cortex was decreased and the latency of the P3 ERP component in the parietal cortex was delayed, compared to the control group during baseline recording conditions. The EtOH group was also more responsive to CRF and NPY. CRF significantly increased cortical power (6-8 Hz) and increased cortical EEG stability in the EtOH group, compared to controls. Additionally, NPY significantly decreased the amplitude of the N1 ERP component in the amygdala of the EtOH group, but not in the control group. This enhanced sensitivity to CRF and NPY following chronic ethanol exposure and abstinence suggests that these peptidergic systems may play a role in the symptomatology of the prolonged abstinence syndrome.

Differences in neurophysiological indices of associative learning in alcohol-preferring and nonpreferring rats.

Alcohol-preferring (P) and -nonpreferring (NP) rats differ in baseline neurophysiological measures as well as in their neurophysiological responses to ethanol. In the present study, these lines of rats were assessed to determine whether they also differ in their neurophysiological responses during an associative learning paradigm. Male P and NP rats were implanted with electrodes in the frontal cortex, parietal cortex, and amygdala. Both groups were then exposed to an associative learning paradigm. During the first five sessions (conditioning phase), an infrequently presented tone was paired with the delivery of a food pellet. A second tone was also presented during these sessions, but this tone was never paired with food pellet presentation. During the second five sessions (extinction phase), neither of the tones were paired with food pellet presentation. Event-related potentials (ERPs) in response to the tones were recorded during both phases of the experiment. During the first session, the latency of the N1 and P3 waves from the cortical lead in response to the food-paired tone was significantly longer in the NP rats than in P rats. In addition, P rats displayed significant increases in the latency of the P2 wave component in the cortex and the P3A wave component in the amygdala in response to changes in the association between food pellet and tone presentation. These data indicate that the P rats were more responsive to changes in the association between food pellet delivery and tone presentation. They also suggest more enhanced associative learning in P rats than in NP rats. This enhanced learning could be an innate trait of P rats or the result of altered learning due to differences in anxiety between P and NP rats.

Presentation of an ethanol-paired stimulus complex alters response patterns during extinction.

It has been hypothesized that environmental stimuli previously paired with ethanol consumption play a role in excessive ethanol intake. This study examined the ability of orally self-administered ethanol to establish a tone-light stimulus complex as a conditioned reinforcer (CSR). Male Long-Evans rats were trained to orally self-administer 10% ethanol (10E) using the sucrose-substitution procedure. During training, a tone-light stimulus complex was paired with ethanol presentation in a stimulus complex paired (SC-paired) group but not in a control group. Responding during extinction in the presence and absence of the stimulus complex was then examined. Following the initiation of ethanol self-administration, 10E maintained greater responding in the SC-paired group compared to the control group. When the stimulus complex was presented contingent on responding during extinction, the rate of extinction was slightly attenuated in the SC-paired group but not in the control group. The altered rate of extinction in the SC-paired group was characterized by: 1) a slight decrease in total session responding over successive days of extinction and 2) a transient attenuation of extinction burst response rate during the first extinction session. These data suggest the stimulus complex could function as a weak CS(R), but overall its ability to maintain lever pressing was minimal.

Appetitive and consummatory behaviors in the control of ethanol consumption: a measure of ethanol seeking behavior.

Models of ethanol self-administration in animals have demonstrated that ethanol can reinforce a variety of behaviors, independent of ethanol's caloric or fluid properties. However, the processes that control self-administration remain unclear. Determining factors related to ethanol seeking behavior, independent of consumption, is central to the concepts of intake regulation. The model described in this article proposes a method to separate the initial appetitive (seeking) behavior from the following consummatory (drinking) behavior to assess each behavior type. Rats were trained to lever press to gain access to a drinking tube connected to a fluid bottle containing either 10% ethanol or 3% sucrose for 20 min. When the response requirement to obtain access to the tube was increased, it was found that both solutions supported the same amount of responding (breakpoint was at approximately a fixed ratio 32 requirement), indicating equal reinforcer strength. However, regardless of the response requirement, if access to the fluids occurred, intakes were not changed. This suggests that factors besides those of reinforcer efficacy are important in controlling the size of the consummatory bout. Based on these findings, we believe that this model will be useful in determining factors related to seeking behaviors and the control of drinking bout size.

Exposure to sucrose-quinine solutions does not increase ethanol consumption.

The taste of ethanol can be aversive or preferred based on prior experience with ethanol consumption. A preference for ethanol's taste is thought to result from the association of ethanol's taste with its neuropharmacological activity. However, acclimation to ethanol's aversive taste may also play a role in increased ethanol consumption following prolonged exposure. The present study examined if acclimation to a bitter-sweet tastant, which has been suggested to share similar taste qualities with ethanol, would increase ethanol intake with only minimal prior experience of an association of ethanol intake with its neuropharmacological activity. Male Long-Evans rats were trained to drink 10% sucrose during 20-min sessions. The consumption of 0-20% ethanol was then determined before and after exposure to a sucrose-quinine solution. Before the sucrose-quinine taste acclimation procedure, the initial intake of sucrose-quinine was low and similar to 5% ethanol. After the acclimation procedure, increases in sucrose-quinine intake, but not ethanol intake, were observed. These data could indicate that any similarity in the taste qualities of sucrose-quinine and ethanol solutions are diminished following exposure to sucrose-quinine. Alternatively, the differential changes in sucrose-quinine and ethanol intake could be the result of being differentially regulated by a combination of taste and postingestive factors. Overall, these data indicate that exposure to sucrose-quinine, which resulted in increased intake of sucrose-quinine, was not sufficient to alter ethanol intake. Rather, exposure to taste and postingestive factors associated with ethanol may be necessary to increase ethanol intake.