Acute tolerance to rate-decreasing effects of single doses of ethanol

Ginsburg, Brett C.; Martínez, Gerardo; Friesenhahn, Gregory; Javors, Martin A.; Lamb, Richard

doi:10.1016/j.physbeh.2008.01.026

Cited by 12 publications

(13 citation statements)

References 24 publications

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“…Also similar to the hypothermic effect, rate-decreasing effects of THC had subsided even though blood levels of THC remained elevated above pre-treatment levels. This is similar to acute tolerance to ethanol effects that we and others previously reported (Ginsburg et al, 2008; Hiltunen and Järbe, 1992). …”

Section: Discussionsupporting

confidence: 92%

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

Ginsburg

Hrubá

Zaki

et al. 2014

Drug and Alcohol Dependence

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Background Recent changes in the legality of cannabis have prompted evaluation of whether blood levels of Δ9-tetrahydrocannabinol (THC) or its metabolites could be used to substantiate impairment, particularly related to behavioral tasks such as driving. However, because marked tolerance develops to behavioral effects of THC, the applicability of a particular threshold of blood THC as an index of impairment in people with different patterns of use remains unclear. Studies relevant to this issue are difficult to accomplish in humans, as prior drug exposure is difficult to control. Methods Here, effects of THC to decrease rectal temperature and operant response rate compared to levels of THC and its metabolites were studied in blood in two groups of monkeys: one received intermittent treatment with THC (0.1 mg/kg i.v.) and another received chronic THC (1 mg/kg/12 h s.c.) for several years. Results In monkeys with intermittent THC exposure, a single dose of THC (3.2 mg/kg s.c.) decreased rectal temperature and response rate. The same dose did not affect response rate or rectal temperature in chronically exposed monkeys, indicative of greater tolerance. In both groups, blood levels of THC peaked 20–60 min post-injection and had a similar half life of elimination, indicating no tolerance to the pharmacokinetics of THC. Notably, in both groups, the behavioral effects of THC were not apparent when blood levels were maximal (20-min post-administration). Conclusion These data indicate that thresholds for blood levels of THC do not provide a consistent index of behavioral impairment across individuals with different patterns of THC exposure.

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Section: Discussionsupporting

confidence: 92%

Blood levels do not predict behavioral or physiological effects of Δ9-tetrahydrocannabinol in rhesus monkeys with different patterns of exposure

Ginsburg

Hrubá

Zaki

et al. 2014

Drug and Alcohol Dependence

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“…These alcohol effects were followed by diminished USV emissions despite continued ingestion of high alcohol intake; a behavioral response pattern consistent with other reports of “tolerance” to alcohol-induced behavioral effects after repeated alcohol experience (Tampier et al, 2000, Batista et al, 2005, Ginsburg et al, 2008, Bell et al, 2011). …”

Section: Discussionsupporting

confidence: 87%

Alcohol‐Preferring P Rats Emit Spontaneous 22‐28 kHz Ultrasonic Vocalizations that are Altered by Acute and Chronic Alcohol Experience

Reno

Thakore

Gonzales

et al. 2015

Alcoholism Clin & Exp Res

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Background Emotional states are often thought to drive excessive alcohol intake and influence the development of alcohol use disorders (AUDs). To gain insight into affective properties associated with excessive alcohol intake, we utilized ultrasonic vocalization (USV) detection and analyses to characterize the emotional phenotype of selectively bred alcohol-preferring “P rats”; an established animal model of excessive alcohol intake. USVs emitted by rodents have been convincingly associated with positive (50–55 kHz) and negative (22–28 kHz) affective states. Therefore, we hypothesized that 50–55 and 22–28 kHz USV emission patterns in alcohol-preferring P rats would reveal a unique emotional phenotype sensitive to alcohol experience. Methods 50–55 kHz frequency-modulated (FM) and 22–28 kHz USVs elicited from male alcohol-preferring P rats were assessed during access to water, 15% and 30% EtOH (v/v). (EtOH; n=12) or water only (Control; n=4) across 8 weeks of daily drinking-in-the-dark (DID) sessions. Results Spontaneous 22–28 kHz USVs are emitted by alcohol-naïve P rats and are enhanced by alcohol experience. During DID sessions when alcohol was not available (e.g., “EtOH OFF” intervals), significantly more 22–28 kHz than 50–55 kHz USVs were elicited, while significantly more 50–55 kHz than 22–28 kHz USVs were emitted when alcohol was available (e.g., “EtOH ON” intervals). In addition, USV acoustic property analyses revealed chronic effects of alcohol experience on 22–28 kHz USV mean frequency, indicative of lasting alcohol-mediated alterations to neural substrates underlying emotional response. Conclusions Our findings demonstrate that acute and chronic effects of alcohol exposure are reflected in changes in 22–28 and 50–55 kHz USV counts and acoustic patterns. These data support the notion that initiation and maintenance of alcohol intake in P rats may be due to a unique, alcohol-responsive emotional phenotype and further suggest that spontaneous 22–28 kHz USVs serve as behavioral markers for excessive drinking vulnerability.

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“…The phenomenon of acute tolerance, as exemplified by the signs and/or symptoms of alcohol influence being more pronounced on the rising part of the BAC curve, is a robust finding and has been reported in many studies [31,32]. In laboratory experiments, the impairment associated with acute alcohol influence usually 1.59 *** 2.17 ** a Risk ratio (RR), ratio of two proportions, calculated as proportion of the one of the non-homicide causes of death divided by the proportion of homicide deaths among those in the post-absorptive phase.…”

Section: Discussionmentioning

confidence: 71%