Biomedical subjects

J M Murphy

Publications and source records attributed to J M Murphy.

At least 37 records · Page 2Linked to original sources

PubMed2001

Effects of concurrent access to multiple ethanol concentrations and repeated deprivations on alcohol intake of alcohol-preferring rats.

BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the voluntary intake of ethanol solutions following a period of alcohol deprivation. Multiple deprivations can prolong the expression of an ADE. This study examined the effects of initial deprivation length, concurrent exposure to multiple ethanol concentrations, and number of deprivation exposures on the magnitude and duration of the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats received 24-hr free-choice access to 10, 20, and 30% ethanol and water for 6 weeks. Rats were then randomly assigned to three groups; one group served as a nondeprived control, whereas the other two groups were initially deprived of ethanol for 2 or 8 weeks. The ethanol solutions were restored to both deprived groups for 2 weeks before the groups were deprived of ethanol for another 2 weeks. This cycle was repeated three times for a total of four deprivations. RESULTS: After the initial ethanol deprivation period, both deprived groups displayed a similar 2-fold increased ethanol intake (g/Kg/day) during the initial 24-hr period when ethanol was restored. Both deprived groups showed greater than 2-fold increases in intake of the 20 and 30% ethanol solutions after re-exposure. Ethanol consumption returned to baseline levels within 2 weeks, before the subsequent deprivation period. Multiple deprivations increased the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure and prolonged the duration of the ADE. In addition, repeated deprivations increased ethanol intake in the first 2-hr period of re-exposure and produced blood ethanol levels in excess of 150 mg/100 ml. CONCLUSIONS: Alterations in the reinforcing and/or aversive effects of alcohol occurred after a single prolonged deprivation and were enhanced with repeated deprivations.

Animals↗

PubMed2001

Alcohol-naïve alcohol-preferring (P) rats exhibit higher local cerebral glucose utilization than alcohol-nonpreferring (NP) and Wistar rats.

BACKGROUND: The present study determined local cerebral glucose utilization (LCGU) rates in alcohol-naïve alcohol-preferring (P), alcohol nonpreferring (NP), and outbred Wistar rats to test the hypothesis that innate differences in functional neuronal activity are present in limbic regions as a result of selective breeding for high-alcohol drinking behavior. METHODS: All procedures were conducted during the dark cycle. 2-[14C]deoxyglucose ([14C]2-DG; 125 microCi/kg) was injected intravenously and timed arterial blood samples were collected during the following 45 min and assayed for glucose and [14C]2-DG content. Rats were then decapitated, the brains removed and frozen to -70 degrees C, and 20 microm coronal sections were prepared for quantitative autoradiographic analysis. RESULTS: Rates of LCGU were determined in 55 regions and subregions, including limbic, cortical, and subcortical structures. LCGU rates were significantly (p < 0.01) higher in several limbic (e.g., ventral tegmental area, nucleus accumbens shell, olfactory tubercle, medial prefrontal cortex, and lateral hypothalamus), cortical (e.g., parietal, temporal, occipital, cingulate, piriform, and entorhinal), and subcortical (e.g., thalamus, habenula, preoptic area, and striatum) regions in P rats, compared with NP and Wistar rats, whereas rates in Wistar rats were higher in a few regions (e.g., CA1 and CA3 regions of the posterior hippocampus) than NP rats. CONCLUSIONS: The data suggest that selective breeding for high-alcohol drinking produces intrinsically higher functional neuronal activity in the central nervous system regions of the high-alcohol consuming P line compared with low-alcohol drinking NP or Wistar rats, although these differences may not generalize to other rat lines selectively bred for divergent alcohol drinking.

Alcoholism↗

PubMed2000

A 40-year perspective on the prevalence of depression: the Stirling County Study.

BACKGROUND: According to epidemiologic studies that use recall of lifetime episodes, the prevalence of depression is increasing. This report from the Stirling County Study compares rates of current depression among representative samples of adults from a population in Atlantic Canada. METHODS: Sample sizes were 1003, 1201, and 1396 in 1952, 1970, and 1992, respectively. The depression component of the study's method, the DPAX (DP for depression and AX for anxiety), was employed. The original procedure (DPAX-1) was applied in all years. A revision (DPAX-2) was used in 1970 and 1992. The Diagnostic Interview Schedule (DIS) was also used in 1992. RESULTS: With the DPAX-1, the overall prevalence of current depression was steady at 5% over the 2 early samples but declined in 1992 because of vernacular changes referring to dysphoria. The DPAX-2 gave a stable overall prevalence of 5% in the 2 recent samples, but indicated that women and younger people were at greater risk in 1992 than in 1970. The DIS, like the DPAX-2, found a current 1992 rate of 5% for major depressive episodes combined with dysthymia. Recalled lifetime rates using the DIS showed the same profile interpreted in other studies as suggesting an increase in depression over time. CONCLUSIONS: Three samples over a 40-year period showed a stable current prevalence of depression using the DPAX methods that was comparable in 1992 with the current rates using the DIS. This casts doubt on the interpretation that depression is generally increasing. Within the overall steady rate observed in this study, historical change was a matter of redistribution by sex and age, with a higher rate among younger women being of recent origin.

Adolescent↗

PubMed2000

A comparison of diagnostic interviews for depression in the Stirling County study: challenges for psychiatric epidemiology.

BACKGROUND: High prevalence rates in psychiatric epidemiologic studies raise questions about whether data-gathering procedures identify transient responses rather than clinical disorders. This issue is explored relevant to depression using data from the Stirling County Study. METHODS: The study's customary method, the DPAX (DP for depression and AX for anxiety) was compared with the Diagnostic Interview Schedule (DIS), both of which were administered to a sample of 1396 subjects selected in 1992. Reasons for discordance were analyzed, and demographic correlates of responses to questions about dysphoria were examined. These lay-administered interviews were then compared with clinician-administered interviews that used the Structured Clinical Interview for DSM-III-R (SCID) with 139 subjects. The kappa statistic and logistic regression were used for statistical assessment. RESULTS: For the level of agreement between the DPAX and the DIS for current and lifetime depression, kappa = 0.40 and kappa = 0.33, respectively. Subjects diagnosed only by the DPAX tended to have less education than those diagnosed only by the DIS. Some idioms for dysphoria seemed to work better than others. Using SCID interviews as a clinical standard, the DPAX had 15% sensitivity and 96% specificity and the DIS had 25% sensitivity and 98% specificity. CONCLUSIONS: Comprehension of an interview can be improved by using multiple questions for dysphoria and a simpler mode of inquiry. Clinician-administered interviews tend to corroborate disorders identified in lay-administered interviews but suggest that survey methods underestimate prevalence. Further research is needed to evaluate the validity of both types of interviews, but evidence from a 16-year follow-up evaluation indicates that depression diagnosed by the DPAX is a serious disorder in terms of morbidity and mortality.

Adult↗

PubMed2000

Chilaiditi's syndrome and obesity.

Hepatodiaphragmatic interposition (HDI) of the colon or small intestine (Chilaiditi's syndrome) is more prevalent in the elderly and in men. The reason for this is unclear. In obese individuals, fat deposition between the liver and colon widens this potential space, and this may be an important factor in the etiology of this condition. As men store more fat intra-abdominally than women, this may explain the increased prevalence in men. This study was performed to investigate the relationship between Chilaiditi's syndrome and obesity. A total of 850 abdominal CT examinations were assessed for the presence of HDI of the colon or small intestine, and 10 patients with Chilaiditi's syndrome were identified. The present Body Mass Index (BMI) and the highest BMI in the past was recorded for each patient. Eight of the 10 patients were male; five had a BMI greater than 28.5 and three had a BMI between 25 and 27.5 at some period in their lives. Obesity may be a causative factor in the etiology of Chilaiditi's syndrome, and the difference in fat deposition between men and women may explain its increased prevalence in men.

Aged↗

PubMed2000

An in vivo model for load-modulated remodeling in the rabbit flexor tendon.

This study tested the hypothesis that eliminating in vivo compression to the wrap-around, fibrocartilage-rich zone of the flexor digitorum profundus tendon results in rapid depletion of fibrocartilage and changes in its mechanical properties, microstructure, extracellular matrix composition, and cellularity. The right flexor digitorum profundus tendons of 2.5-3-year-old rabbits were translocated anteriorly to eliminate in vivo compression and shear to the fibrocartilage zone and, at 4 weeks after surgery, were compared with tendons that had sham surgery and with untreated tendons. The translocated tissue showed a significant increase in equilibrium strain under a compressive creep load (p < 0.05). The thickness and area of the fibrocartilage zone also decreased significantly (p < 0.05). The nuclear density decreased by 40% in the fibrocartilage zone (p < 0.005); however, nuclear shape and orientation were not significantly altered. Glycosaminoglycan content in the fibrocartilage zone was also depleted by 40% (p < 0.02). The tightly woven basket weave-like mesh of collagen fibers in the zone appeared more loosely organized, suggesting matrix reorganization due to translocation. Moreover, immunoreactive type-II collagen and link protein in the fibrocartilage zone also decreased. With use of this unique in vivo model, this research clearly elucidates how changing tissue function (by removing compressive forces) rapidly alters tissue form.

Animals↗

PubMed2000

Regional heterogeneity for the intracranial self-administration of ethanol within the ventral tegmental area of female Wistar rats.

RATIONALE: Because current findings indicate that the selectively bred alcohol-preferring P line of rats self-administers 50-200 mg% ethanol (EtOH) directly into the ventral tegmental area (VTA), whereas the alcohol-nonpreferring NP line does not, it is important to determine whether unselected, common stock rats would self-administer EtOH directly into the VTA. In addition, because neuroanatomical and self-administration studies indicate that the VTA may be functionally heterogeneous, the present study was designed to determine whether there were subregional differences within the VTA for the intracranial self-administration (ICSA) of EtOH. OBJECTIVES: The objective of this study was to employ the ICSA technique to determine whether adult female Wistar rats would self-administer EtOH directly into the VTA, and whether regional heterogeneity existed for EtOH self-infusion within the VTA. METHODS: Following surgery to implant guide cannulae aimed at either the posterior or anterior VTA, subjects were placed in standard experimental chambers equipped with an 'active lever' [fixed ratio (FR)1 schedule of reinforcement], which caused the delivery of the infusate, and an 'inactive lever', which had no programmed consequence. Subjects were assigned to groups that self-administered either artificial cerebrospinal fluid (aCSF) throughout, or 100-400 mg% EtOH for the first four sessions (acquisition), aCSF in sessions 5 and 6 (extinction), and EtOH again during session 7 (reinstatement). RESULTS: During the four acquisition sessions, rats with posterior VTA placements readily self-administered 200 mg% and 250 mg% EtOH and discriminated between the active and inactive levers. These subjects also demonstrated extinction, when aCSF was substituted for EtOH, and reinstatement when EtOH was reintroduced. Rats with posterior VTA placements self-infused 300 mg% and 400 mg% EtOH, and demonstrated lever discrimination only during the initial acquisition sessions. In contrast, rats with anterior VTA placements did not self-administer EtOH. CONCLUSIONS: The findings suggest that EtOH is reinforcing within the posterior VTA of Wistar rats, and the VTA is a functionally heterogeneous structure with regard to EtOH reinforcement.

Animals↗

PubMed2000

An assessment of novelty-seeking behavior in alcohol-preferring and nonpreferring rats.

This study examined novelty-seeking behavior in rat populations selectively bred for high and low alcohol-drinking behavior. In Experiment 1, and "odor-enhanced" novel environment produced greater behavioral activation in P compared to NP rats. In Experiment 2, the activity of high alcohol-drinking P and HAD rats was enhanced to a greater extent following the presentation of novel odors in a familiar arena, compared to the NP and LAD rats. The results suggest that, when measuring locomotor activity, alcohol-preferring rats are more reactive to novelty than their nonpreferring counterparts. Experiments 3 and 4, however, did not support the hypothesis that novelty seeking is associated with genetic vulnerability to high alcohol-drinking behavior. When measuring nose-poking behavior in response to novel odors and preference for a novel vs. a familiar chamber, behavior of the preferring lines did not differ from that of the nonpreferring lines, although P rats were more active in the place-preference paradigm. The overall results indicate that the relationship between novelty and alcohol drinking is only modestly associated, and is observed under specific conditions. Moreover, this study underscores the importance of using multiple measures when assessing complex behaviors such as novelty seeking.

Alcohol Drinking↗

PubMed2000

Effects of ethanol on startle responding in alcohol-preferring and -non-preferring rats.

The objectives of the present study were to determine (a) if differences exist between the selectively bred alcohol-preferring (P) and -non-preferring (NP) lines of rats in the acoustic startle response (ASR) and prepulse inhibition (PPI), and (b) the effects of ethanol on these measures. Alcohol-naïve adult female P and NP rats received a single i.p. injection of saline or ethanol (0.25, 0.5, 1. 0, or 1.5 g/kg) and were placed in the startle apparatus 10 min later. After a 5-min acclimation period, rats received five alternating trials of a startle stimulus alone (SSA) (115-dB white noise) or a PPI trial (90-dB white noise preceding a 115-dB white noise). Analysis of the ASR revealed that P rats exhibited higher startle amplitudes than did NP rats with saline injections. The 0. 5-g/kg ethanol dose reduced the startle amplitude in P, but not NP, rats. The 1.0- and 1.5-g/kg ethanol doses nearly abolished the ASR in the NP line, whereas only the highest ethanol dose had this effect in the P line. Vehicle-treated P and NP rats exhibited comparable PPI levels, but only P rats showed a significant disruption (30%) at the 0.50-g/kg ethanol dose. Neither P nor NP rats were affected by ethanol treatment at the 0.25-g/kg dose. Overall, the results suggest that: (a) the difference in baseline ASR may indicate line differences in the neurocircuitry mediating this response, possibly reflecting higher innate levels of emotional reactivity in the P line; (b) the P line may be more sensitive than the NP line to the effects of ethanol in reducing emotional reactivity; and (c) low-dose ethanol may have a greater disruptive effect on sensorimotor gating mechanisms in the P than NP rat.

Alcohol Drinking↗

PubMed2000

Sensitivity and tolerance to the motor impairing effects of moderate doses of ethanol.

The present study assessed sensitivity and the development of tolerance to the motor impairing effects of moderate doses of ethanol, using an oscillating bar task. Adult male Wistar rats were trained for 5 consecutive days to stay on the oscillating bar for 120 s to avoid a 0.5-mA foot shock. On the 5 consecutive test days, animals were injected once a day with ethanol (ip: 1.0, 1.25, or 1.5 g/kg) and tested at 15 min intervals until recovery to the 120 s criterion. On test day 1, rats in the 1.5 g/kg group took significantly longer to recover (81+/-9 min; mean+/-S.E.M.) than did animals in the 1.25 (49+/-9 min) and 1.0 (29+/-5 min) g/kg groups. Tolerance developed to all doses by test day 3, with the 1.5, 1.25, and 1.0 g/kg groups reaching criterion in significantly shorter times (42+/-8, 31+/-5, and 18+/-2 min, respectively), as compared to test day 1. BACs associated with recovery time on test day 3, for the 1.5 g/kg group, were significantly higher than the BACs associated with recovery time on test day 1. The data suggest that the oscillating bar task can be used to measure the acute ataxic effects of ethanol, across a narrow range of moderate ethanol doses, and, as well, the development of tolerance to the motor impairing effects of these ethanol doses.

Animals↗

PubMed2000

Acoustic startle and fear-potentiated startle in alcohol-preferring (P) and -nonpreferring (NP) lines of rats.

The objective of the present study was to determine whether alcohol-preferring P and -nonpreferring NP rats differ in their acoustic startle response and in fear-potentiated startle. In Experiment 1, male P and NP rats were tested on the startle response to acoustic stimuli ranging from 90-115 dB. Experiments 2 and 3 examined fear-potentiated startle and extinction of the response. In Experiment 2, rats received two light foot shock training sessions separated by 3-4 h. Testing consisted of ten acoustic startle (115 dB) and fear-potentiated startle (light preceding the acoustic startle) presentations administered every 24 h for 9 consecutive days. To test potentiated startle learning under reduced training conditions, a single training session was administered in Experiment 3, and a single within-session extinction test of 50 startle and 50 potentiated startle trials occurred the following day. Results of Experiment 1 indicated that P and NP rats did not differ in startle at any of the acoustic intensities tested. Following fear-potentiated startle conditioning in Experiment 2, however, both acoustic startle and potentiated startle responding were consistently greater in P than NP rats over most of the first 6 test days with P rats having approximately a 100% greater acoustic startle and 50-100% greater potentiated startle response. Moreover, following a single training session in Experiment 3, only P rats showed significant fear-conditioned startle. Additionally, P rats exhibited a 50-100% elevated acoustic startle response over that observed in NP rats. Taken together, the data indicate that, although experimentally naive male P and NP rats show similar acoustic startle responses, P rats become more responsive to both startle-alone and potentiated startle stimuli following fear conditioning. The change in general startle reactivity of the P rat following aversive conditioning, along with facilitated light foot shock learning, suggests that stress exposure may be an important variable in examining associations between anxiety and alcohol drinking behavior.

Acoustic Stimulation↗

PubMed2000

What progress has been made in meeting the needs of seriously maltreated children? The course of 200 cases through the Boston Juvenile Court.

OBJECTIVES: The study examined child, parent, and case characteristics in a sample of 200 cases of serious child maltreatment brought before the Boston Juvenile Court (BJC) on Care and Protection petitions in 1994. Whether recent changes in Massachusetts law have been effective in reducing delays in adjudication and helping children achieve permanent placements more quickly was also examined. METHOD: Data were abstracted from court records by the research team. The 200 cases were followed prospectively for 4 years. Retrospective data on the families' previous involvement with the protective service system were also abstracted from the records. Data from the 1994 cases were compared to that obtained from a sample of cases brought before the BJC in 1985-1986. RESULTS: Children permanently removed from parental custody in the 1994 sample required less time post-disposition to achieve permanent placements. However, overall, time frames for the 1994 cases remained remarkably similar to those in 1985-1986: children were in the protective service system an average of 5 years; cases required an average of 1.6 years in court; and half of the children permanently removed from parental custody were still in "temporary" foster care at 4-year follow-up. CONCLUSIONS: Although some improvements have occurred since 1985-1986, the system still fails to meet the needs of seriously maltreated children to achieve permanent placements promptly. The implications of the findings for system reform are discussed.

Adolescent↗

PubMed2000

Effects of 5-HT(3) receptor antagonists on daily alcohol intake under acquisition, maintenance, and relapse conditions in alcohol-preferring (P) rats.

Previous research indicated that 5-HT(3) antagonists can reduce ethanol drinking in rats, but drinking conditions and other environmental manipulations influenced the efficacy of these antagonists. The current experiments were conducted to examine the effects of the 5-HT(3) antagonists MDL 72222 (MDL) or ICS 205-930 (ICS) on 24-h ethanol (10% v/v) consumption during acquisition, maintenance, and following a period of deprivation in selectively bred high alcohol-preferring (P) male rats. In an analysis of the acquisition of ethanol consumption, daily injections of MDL (1 mg/kg; s.c.) or ICS (1 or 5 mg/kg) were administered to separate groups of P rats during the initial 10 days of ethanol exposure. To examine the maintenance of ethanol drinking, these same groups of rats were allowed access to ethanol for 21 days with no pharmacological manipulations, and were then administered either saline or the 5-HT(3) antagonist. To examine the effects of a 5-HT(3) antagonist on relapse of ethanol drinking, another group of P rats was allowed access to ethanol for 6 weeks and was then deprived of ethanol for 3 weeks. Prior to ethanol reinstatement, rats were treated chronically (seven daily injections) or acutely with MDL (1 mg/kg), saline, or received no injections. MDL (1 mg/kg) and ICS (1 or 5 mg/kg) reduced ethanol intake during acquisition (60-80%) and during maintenance drinking (35-70%) in P rats pretreated with saline during acquisition. However, in rats pretreated with MDL or ICS during acquisition, there was a significant reduction in the effectiveness of either MDL or ICS to reduce ongoing ethanol drinking. Neither acute nor chronic treatment with 1 mg/kg MDL altered the 80% increase in ethanol consumption observed on the first day of reinstatement following a 3-week deprivation period. However, in a follow-up study, acute treatment with MDL (3 mg/kg) or ICS (5 mg/kg) did prevent the 80% increase in ethanol consumption observed on the first day of reinstatement. Overall, the results suggest that 5-HT(3) receptors are involved in the acquisition and maintenance of 24-h ethanol drinking, and that neuroadaptations may occur as a result of chronic treatment with 5-HT(3) antagonists, or during prolonged alcohol deprivation, which alter the involvement of these receptors in regulating alcohol drinking in the P rat.

Alcohol Drinking↗

PubMed2000

Incidence of depression in the Stirling County Study: historical and comparative perspectives.

BACKGROUND: The Stirling County Study provides a 40-year perspective on the epidemiology of psychiatric disorders in an adult population in Atlantic Canada. Across samples selected in 1952, 1970 and 1992 current prevalence of depression was stable. This paper concerns time trends in annual incidence as assessed through cohorts selected from the first two samples. METHODS: Consistent interview data were analysed by a computerized diagnostic algorithm. The cohorts consisted of subjects at risk for a first depression: Cohort-1 (N = 575) was followed 1952-1970; Cohort-2 (N = 639) was followed 1970-1992. Life-table methods were used to calculate incidence rates and proportional hazards procedures were used for statistical assessment. RESULTS: Average annual incidence of depression was 4.5 per 1000 for Cohort-1 and 3.7 for Cohort-2. Differences by gender, age and time were not statistically significant. The stability of incidence and the similarity of distribution by gender and age in these two cohorts corresponds to findings about the two early samples. In contrast, current prevalence in the recent sample was distributed differently and showed an increase among women under 45 years. CONCLUSIONS: The stability of the incidence of depression emphasizes the distinctive characteristics of current prevalence in the recent sample and suggests that the dominance of women in rates of depression may have occurred among those born after the Second World War. The results offer partial support for the interpretation of an increase in depression based on retrospective data in other recent studies but they indicate that the increase is specific to women.

Adolescent↗

PubMed2000

Utility of psychosocial screening at a school-based health center.

School-based health centers (SBHC) have substantial potential to improve the recognition and treatment of adolescents' mental health problems. This study was undertaken as a quality improvement project to evaluate utility of the Pediatric Symptom Checklist when completed by youth (PSC-Y) among 383 adolescents seen at a SBHC, and the extent to which identification of psychosocial dysfunction and referral to mental health services improved academic functioning. Adolescents identified by the PSC-Y were significantly more likely to be insured by Medicaid, be a teen-age parent, and to have higher rates of absenteeism and tardiness in comparison to those not identified. Adolescents identified with the PSC-Y who were referred to mental health services significantly decreased their rates of absences and tardiness. Study results provide support for the utility of psychosocial screening and referral in the SBHC environment in facilitating recognition and treatment of adolescent mental health problems and improving student academic functioning.

Absenteeism↗

PubMed2000

Effects of transportation and delay in processing on the stability of nutritional and metabolic biomarkers.

The effects of transportation and delay in processing of blood samples on the concentration of biomarkers are significant in epidemiological studies for which specimens are collected from participants at locations other than a designated center or laboratory. These sources of variability in measurement were studied by collecting two sets of blood samples from 51 men between 26 and 50 years of age. The first set was sent immediately to the laboratory for processing. The second set was transported by car for one hour and then returned to the laboratory for processing. Both sets were stored together at -80 degrees C until the end of the study. Several blood constituents were evaluated. Vitamins, liver enzymes, and electrolytes showed no changes in concentration after transport by car for one hour. There were decreases in the concentrations of red and white blood cells, high-density-lipoprotein cholesterol, glucose, and creatinine after transportation. The transported total cholesterol, total testosterone, free testosterone, alkaline phosphatase, total bilirubin, and thiobarbituric acid-reactive substances increased in concentration. Although transportation and delay in processing of blood samples do not appear to greatly impact relative risk estimates, epidemiologists should be aware of these potential sources of variability in measurement and consider the consequences in their particular study.

Adult↗

PubMed2000

Alcohol deprivation effect is prolonged in the alcohol preferring (P) rat after repeated deprivations.

BACKGROUND: The alcohol deprivation effect (ADE) is a temporary increase in the ratio of ethanol/total fluid intake and the voluntary intake of ethanol solutions over baseline drinking conditions when ethanol access is reinstated after a period of alcohol deprivation. The ADE has been posited to be an animal model for alcohol craving. The current study examined the effects of initial deprivation length and number of deprivation exposures on the ADE in alcohol-preferring (P) rats. METHODS: Adult female P rats received 24-hr free-choice access to 10% (v/v) ethanol and water for 6 weeks. Rats were then randomly assigned to five groups deprived of ethanol for 0 (control), 2, 4, 6, or 8 weeks (W). All deprived groups were then given 24-hr access to ethanol for 2 weeks before being deprived of ethanol for another 2 weeks. RESULTS: After the initial ethanol deprivation period, the deprived groups displayed a similar 2-fold ADE (e.g., 4-W group; 4.6 +/- 0.5 for baseline vs. 10.5 +/- 0.3 g/kg/day for the 1st reinstatement day) during the initial 24-hr period. Ethanol consumption began to return to control levels 48 (7.1 +/- 0.4 g/kg/day) and 72 (6.4 +/- 0.4 g/kg/day) hrs later. In addition, each deprived group showed increases in the ratio of ethanol/total fluid intake upon reinstatement, and there was a tendency for sustained higher ethanol intake ratios during the first 3 postexposure days for the 4-, 6-, and 8-W groups, but only during the first 2 reinstatement days for the 2-W group. The second deprivation did not increase the magnitude of the ADE over that observed in the first deprivation during the initial 24-hr period of re-exposure, but it did prolong the duration of the ADE into the 2nd and 3rd reinstatement day for the 2-, 4-, and 6-W groups and into the 5th reinstatement day for the 8-W group. CONCLUSIONS: Equivalent robust ADEs can be seen in P rats with deprivation periods of 2-8 W, which suggests that the ADE has a rapid onset and is not affected by the durations of deprivation that were tested. The duration of the ADE was prolonged in P rats exposed to a second deprivation period, suggesting that factors associated with the ADE phenomenon could be strengthened by repeated deprivations.

Alcohol Drinking↗

PubMed2000

Involvement of dopamine D2 autoreceptors in the ventral tegmental area on alcohol and saccharin intake of the alcohol-preferring P rat.

BACKGROUND: The ventral tegmental area (VTA) dopamine (DA) system is considered to be involved in mediating the actions of ethanol (EtOH). The objective of the present study was to examine the role of VTA DA D2 receptors in regulating EtOH intake of alcohol-preferring P rats. METHODS: EtOH (10% v/v) and saccharin (SACC, 0.0125% g/v) intake during 2 hr of limited access was assessed after microinjections of the D2 agonist quinpirole and the D2 antagonist sulpiride into the anterior VTA (AVTA) of female P rats. Both EtOH-SACC alternate-day-access conditions and daily availability of EtOH and SACC solutions to separate groups of subjects were used. A second D2 agonist, quinelorane, and coadministration of 2.0 microg sulpiride with 2.0 microg quinpirole were tested in animals given limited access to EtOH. Finally, the effects of quinpirole injected 2 mm dorsal to the VTA and within the posterior VTA (PVTA) were assessed under EtOH-SACC alternate-day-access conditions. RESULTS: Microinjections of 2.0-6.0 microg quinpirole into the AVTA dose dependently decreased EtOH intake 40-80% during the first 30 min of the limited access sessions but did not alter SACC intake. Injections of 2.0-4.0 microg quinelorane into the AVTA also reduced EtOH intake in the first 30 min. Administration of 0.5-2.0 microg sulpiride into the AVTA had no effect on either EtOH or SACC intakes but did attenuate the effects of quinpirole on reducing EtOH intake. Injections of 2.0-4.0 quinpirole 2 mm dorsal to the VTA did not alter EtOH or SACC intakes. Posterior VTA injections of quinpirole decreased EtOH and SACC intakes approximately 25-30% and 60-70%, respectively, in the first 30 min. None of the treatments altered intakes during the 30-120 min period. CONCLUSIONS: The data suggest that DA neuronal activity within the AVTA may be important for maintaining EtOH drinking in P rats, whereas DA neuronal activity within the PVTA may be involved in regulating general drinking and/or motivational behaviors. Overall, the results confirm the involvement of mesolimbic DA in EtOH self-administration and suggest that there is functional heterogeneity within the VTA regulating drinking behavior of the P rat.

Alcohol Drinking↗