Biomedical subjects

R J Lamb

Publications and source records attributed to R J Lamb.

At least 19 recordsLinked to original sources

PubMed2006

Effects of chronic fluvoxamine on ethanol- and food-maintained behaviors.

Acute treatment with fluvoxamine reduces responding for ethanol more than responding for food. However, pharmacotherapy for alcoholism is likely to require chronic treatment. These experiments were performed to assess the effects of chronic fluvoxamine on ethanol- and food-maintained behaviors. Effects of chronic fluvoxamine (10 and 17.8 mg/kg/dayx30 days) on ethanol- and food-maintained responding were compared to responding during saline treatment in four Sprague-Dawley rats responding for ethanol and food under a multiple fixed-ratio 5, fixed-ratio 5 schedule. In two subjects, chronic fluvoxamine reduced ethanol-maintained responding more than food-maintained responding; however this effect was transient. In another subject, treatment persistently decreased food-maintained responding relative to ethanol-maintained responding. Finally, in one subject, fluvoxamine nonspecifically disrupted responding for food and ethanol. Similar to results in humans, outbred Sprague-Dawley rats had differential responses to chronic fluvoxamine. The effect was transient in rats that responded favorably (greater reduction of ethanol relative to food responding), while response reductions persisted throughout treatment in rats that responded unfavorably (greater reduction of food relative to ethanol or nonspecific reductions).

Animals↗

PubMed2006

Fluvoxamine effects on concurrent ethanol- and food-maintained behaviors.

In previous studies, the selective serotonin reuptake inhibitor fluvoxamine preferentially reduced responding for ethanol compared with responding for food under conditions in which each was available alone in separate groups or in the same subjects under a multiple schedule in which baseline response rates were matched. The impact of providing concurrent access to food on pharmacological effects on ethanol self-administration remains largely unexplored. In this study, acute doses of fluvoxamine (3.0-17.8 mg/kg) were administered 30 min before the experimental session to Lewis rats responding under a concurrent fixed-ratio, fixed-ratio schedule of ethanol and food presentation. Ratios for food were adjusted for each subject to provide matched rates of food and ethanol reinforcement across the 30-min session. Although the number of ethanol and food deliveries did not significantly differ under baseline conditions, response rates did differ. Following fluvoxamine administration, responding for food was decreased more than responding for ethanol. This differential effect did not appear to be related to response rate or fixed-ratio size. Thus, the selectivity of fluvoxamine on ethanol- versus food-maintained responding depends on the context in which the behavior occurs. Such results may help explain inconsistencies between preclinical results and those in humans, and could provide insight into the behavioral determinants of pharmacological effects on ethanol self-administration.

Animals↗

PubMed2006

Sources of variation in the interaction between three cereal aphids (Hemiptera: Aphididae) and wheat (Poaceae).

The relative contributions of host plant, herbivore species and clone to variation in the interaction between cereal aphids and wheat were investigated using five clones each of three species, Rhopalosiphum padi (Linnaeus), Sitobion avenae (Fabricius) and Schizaphis graminum (Rondani), on seedlings of two cultivars of Triticum aestivum L. and one cultivar of Triticum durum Desf. More individuals and biomass of R. padi than of the other two species were produced on seedlings. The three wheat cultivars lost similar amounts of biomass as a result of infestation by aphids, with the amount lost depending on aphid species: S. avenae caused the lowest loss in biomass. Variation in aphid biomass production was due mostly to differences among aphid species (70%), less to the interaction between wheat type and aphid species (7%), and least to aphid clone (1%). The specific impact of the aphids on the plants ranged from 1.7 to 3.7 mg of plant biomass lost per mg of aphid biomass gained, being lowest for R. padi and highest for S. graminum. Variation in plant biomass lost to herbivory was due mostly to unknown sources of error (95%), probably phenotypic differences among individual seedlings, with 3% due to aphid species and none attributable to aphid clone. For these aphid-plant interactions, differences among aphid clones within species contributed little to variation in aphid and plant productivity; therefore, a small sample of clones was adequate for quantifying the interactions. Furthermore, one clone of each species maintained in the laboratory for about 200 parthenogenetic generations was indistinguishable from clones collected recently from the field.

Analysis of Variance↗

PubMed2005

Discriminative stimulus effects of gamma-hydroxybutyrate (GHB) in rats discriminating GHB from baclofen and diazepam.

Gamma-hydroxybutyrate (GHB) is a drug of abuse with actions at GHB and GABA receptors. This study tried to increase the selectivity of the discriminative stimulus effects of GHB by training animals to discriminate GHB from compounds that share pharmacological mechanisms with GHB. In comparison with a previous GHB versus saline discrimination (group 1), rats were trained to discriminate GHB (200 mg/kg) either from saline and the GABA(B) agonist baclofen (3.2 mg/kg) (group 2) or from saline, baclofen, and the positive GABA(A) modulator diazepam (1 mg/kg) (group 3). In all groups, GHB produced more than 80% GHB-appropriate responding. Baclofen produced 84% GHB-appropriate responding in group 1 but less than 30% in groups 2 and 3. Diazepam produced 68% GHB-appropriate responding in group 1, 30% in group 2, and only 5% in group 3. The GABA(B) receptor antagonists CGP35348 [3-[aminopropyl(diethoxymethyl)phosphinic acid] and CGP52432 [3-[[[((3,4-dichlorophenyl)methyl]amino]propyl]diethoxymethyl)phosphinic acid] attenuated the discriminative stimulus effects of GHB; CGP35348 did so with similar potency in all groups, but CGP52432 was significantly less potent in groups 2 and 3 than in group 1. In all groups, the GHB antagonist NCS-382 [(2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid] partially attenuated the discriminative stimulus effects of GHB. The selective GHB receptor ligand UMB86 (4-hydroxy-4-napthylbutanoic acid sodium) tended to attenuate the discriminative stimulus effects of GHB more in group 3 than in the other groups. The finding that animals can discriminate GHB from baclofen is further evidence that the effects of GHB and baclofen are not identical. Effects that GHB does not share with baclofen may involve GHB receptors or differential interactions with GABA(B) receptors.

4-Butyrolactone↗

PubMed2005

Effects of fluvoxamine on a multiple schedule of ethanol- and food-maintained behavior in two rat strains.

RATIONALE: Previous studies show that selective serotonin reuptake inhibitors (SSRIs), including fluvoxamine, have a greater effect on ethanol-maintained responding compared with an alternative reinforcer. However, none of these studies matched baseline responding for reinforcers. Because behavioral effects of many drugs depend on the baseline response rate, the preferential effects of SSRIs may be due to different baseline response rates. OBJECTIVES: Fluvoxamine effects on ethanol- and food-maintained responding were compared using a multiple schedule of behavior, providing matched baseline responding and allowing within-subject analysis in two strains of rats. METHODS: The multiple schedule consisted of three consecutive 5-min, fixed-ratio five components (Food1, Ethanol, Food2). Fluvoxamine (3-30 mg/kg, i.p.) was administered 30 min presession. In Lewis rats, fluvoxamine effects were determined at several available ethanol concentrations [8, 16, 32, and 8% (w/v) redetermination]. In Sprague-Dawley rats, fluvoxamine effects were determined when the available ethanol concentration was 8% (w/v). RESULTS: Baseline responding was stable and well matched under all conditions except 32% ethanol, when responding for ethanol was lower than for food. After the administration of 17.8 mg/kg fluvoxamine, ethanol-maintained responding was 15-33% lower than food-maintained responding in four of the five conditions tested. Breath ethanol assessments indicated that rats had blood ethanol levels of 33 mg/dl following responding for 8% ethanol. CONCLUSIONS: These results are in agreement with previous findings that SSRIs preferentially reduce ethanol-maintained responding and suggest this is not likely due to different baseline levels of responding between the comparison conditions. Further, these results support the hypothesis that alteration of synaptic serotonin can modulate ethanol reinforcement.

Animals↗

PubMed2005

Shaping reduced smoking in smokers without cessation plans.

Most smokers do not plan to quit in the next 6 months. The authors previously demonstrated that percentile schedules shape lower breath carbon monoxide (BCO) levels in smokers trying to quit (R. J. Lamb, A. R. Morral, K. C. Kirby, M. Y. Iguchi, & G. Galbicka, 2004). In that study, the authors set reinforcement criteria based on the 9 most recent samples. In this study, the authors examined whether a more responsive procedure using the 4 most recent samples is more effective in smokers not trying to quit. Following institution of the contingencies in both groups, BCO levels were substantially reduced, and readiness to quit and cessation self-efficacy increased. However, more individuals in the 4-sample window group achieved a BCO level below 4 ppm, indicating recent abstinence. These individuals did so more rapidly and for a greater number of visits.

Adolescent↗

PubMed2005

The prevalence and associated features of posterior embryotoxon in the general ophthalmic clinic.

PURPOSE: To estimate the prevalence of posterior embryotoxon (PE) in the general ophthalmic clinic and to identify any features of PE that suggest that it is pathological rather than physiological. METHODS: Over 700 consecutive patients of all ages were examined with the slit lamp during their routine eye clinic appointment. Patients with posterior embryotoxon were invited to return for full ocular examination including keratometry, corneal topography, and gonioscopy. RESULTS: In all, 49 out of 723 patients were found to have PE. This gives a prevalence of 6.8% with an age range of 18 months to 95 years. There was a higher prevalence in the younger age group of 22.5% (age range 18 months to 20 years) compared to 5.9% in the older age range (21-95 years). A total of 29 patients with PE returned for further examination. Six patients had glaucoma (two with Axenfeld's syndrome and one with aniridia), and one had ocular hypertension. In all, 20 patients had bilateral PE on slit-lamp examination, which increased to 24 with gonioscopy. The majority of the PE was seen temporally (97.9%) and limited to a few clock hours. Gonioscopy showed that eight patients with PE had associated inferior pigmentation of schwalbes line. CONCLUSION: This large series found the prevalence of PE the general ophthalmic clinic to be 6.8%. Its presence should prompt careful anterior segment examination, including gonioscopy, to identify any associated abnormalities that may carry a risk of glaucoma. Children should also be assessed for any associated systemic or genetic abnormality.

Abnormalities, Multiple↗

PubMed2005

Predictors of initial abstinence in smokers enrolled in a smoking cessation program.

The present study examined the relative contribution of nicotine dependence, self-efficacy, and stages of change variables in predicting the initial abstinence of 102 smokers enrolled in a smoking cessation program. Over half the participants were female, the majority were White, and about half were married or living with a partner Data were collected between 2000 and 2002. When smoking abstinence was defined as having a breath carbon monoxide (CO) level <4 ppm within 24 hours of enrollment in the study, low nicotine dependence and a higher level of contemplation both predicted abstinence. When other potentially confounding variables were included in the analysis, neither nicotine dependence nor contemplation was predictive of abstinence. When abstinence was defined as the number of study baseline days in which the participant had a breath CO level <4 ppm, multiple-regression analysis revealed that self-efficacy predicted abstinence. Self-efficacy remained predictive when other potentially confounding variables were included in the analysis. These results suggest that all three types of constructs are useful in predicting initial smoking abstinence.

Adult↗

PubMed2005

Alphaxalone and epiallopregnanolone in rats trained to discriminate ethanol.

BACKGROUND: Neurosteroids with a 3 alpha-hydroxy orientation share pharmacological effects with ethanol, increase in brain after ethanol administration, and may mediate ethanol effects. 3beta-hydroxy neurosteroids antagonize in vitro and some, but not all in vivo effects of ethanol and 3 alpha-hydroxy neurosteroids. METHODS: We assessed the discriminative stimulus and rate altering effects of alphaxalone, a 3 alpha-hydroxy neurosteroid, and epiallopregnanolone, a 3beta-hydroxy neurosteroid, in rats trained to discriminate either 0.8 g/kg or 1.2 g/kg ethanol. The ability of epiallopregnanolone to antagonize the discriminative stimulus or rate-altering effects of ethanol or alphaxalone was also assessed. RESULTS: Ethanol had similar discriminative ED50s (0.5 g/kg) in both groups; however rats trained with the lower ethanol dose were more sensitive to rate-decreasing effects of ethanol. Alphaxalone occasioned ethanol-appropriate responding in both training groups, although less effectively in rats trained on the lower ethanol dose (maximum 65% versus 80% ethanol-appropriate responding). No difference in sensitivity to the rate-decreasing effects of alphaxalone was present between groups. Epiallopregnanolone did not reliably occasion ethanol-appropriate responding in either training group, and rats trained on the lower ethanol dose were slightly more sensitive to epiallopregnanolone rate decreasing effects. Epiallopregnanolone did not alter any effects of ethanol or alphaxalone. CONCLUSIONS: Our results agree with previous reports that 3 alpha-hydroxy neurosteroids occasion ethanol-appropriate responding, while 3beta-hydroxy neurosteroids do not; as well as reports showing no antagonism of the discriminative stimulus or rate-suppressant effects of ethanol or 3 alpha-hydroxy neurosteroids by 3beta-hydroxy neurosteroids. Results of the present study demonstrate that ethanol and 3 alpha-hydroxy neurosteroids share discriminative stimulus effects. However, these results are inconsistent with the hypothesis that such neurosteroids mediate the discriminative stimulus of ethanol.

Animals↗

PubMed2005

Fluvoxamine and desipramine on fixed-ratio responding: effects of reinforcement magnitude.

Fluvoxamine, a serotonin reuptake blocker, was previously shown to decrease ethanol-maintained behavior at doses lower than those needed to decrease food-maintained behavior. While these effects could have been due to different response rates and histories of the two groups being compared, a subsequent study found differential effects using a within-subjects design, in which rates of responding were well equated. Another explanation for such differential effects is that food and ethanol reinforcement differ in a quantitative fashion. This is difficult to resolve when comparing between behaviors maintained by different events. To examine how such quantitative differences in reinforcement magnitude might influence the effects of fluvoxamine, we used a multiple schedule of fixed-ratio 30 responding in the pigeon. In each of the three fixed-ratio 30 components, behavior was maintained by a different duration of grain presentation (2, 4, and 8 s). The effects of fluvoxamine and also desipramine were examined. Both dose-dependently decreased fixed-ratio responding. Their effects were independent of the duration of grain presentation maintaining responding. These results do not support the idea that the differential effects of fluvoxamine on ethanol-maintained behavior, as compared with food-maintained behavior, are a result of quantitative differences in reinforcement magnitude.

Adrenergic Uptake Inhibitors↗

PubMed2004

Shaping smoking cessation using percentile schedules.

Behavioral interventions that provide incentives contingent upon abstinence are effective addiction treatments. Nevertheless, these treatments often fail for individuals whose recent behaviors are very different from those reinforced. These hard-to-treat individuals may require shaping to achieve abstinence. We used percentile schedules to shape smokers' delivery of breath samples indicative of recent smoking abstinence (breath carbon monoxide (BCO) <4 ppm). Percentile schedules deliver incentives to current behaviors proximal to the target. Participants (N = 102) were assigned to treatments delivering incentives for breath COs at or below the 10th, 30th, 50th, or 70th percentile of recent breath COs. Each condition effectively ensured contact with available contingencies, and resulted in BCO <4 ppm in >90% of the 30th, 50th and 70th percentile groups versus 63% in the 10th percentile. The 30th, 50th and 70th percentiles were especially effective in a sub-sample of hard-to-treat participants who did not deliver a breath CO <4 ppm during an initial abstinence test or during a nine-visit baseline period, suggesting the value of shaping for this important sub-sample.

Adult↗

PubMed2004

Convergent and concurrent validity of the Contemplation Ladder and URICA scales.

This study examined the convergent and concurrent validity of the Contemplation Ladder and the University of Rhode Island Change Assessment (URICA). Intake data of participants recruited into two concurrent studies were analyzed. One group (n=77) had no plans to quit smoking within the next 6 months, while a second group (n=106) had definite plans to quit. The groups did not differ on any demographic variables except employment status. Contemplation Ladder scores for the entire sample (n=183) correlated positively with the URICA Contemplation and Action subscale scores but negatively with Precontemplation subscale scores. The Contemplation Ladder also correlated positively with the URICA Composite score. Additionally, participants seeking to quit within the next 6 months had significantly higher Contemplation Ladder and URICA Contemplation, Action, and Composite scores, but lower Precontemplation scores than participants not seeking to quit. Controlling for employment status did not change the pattern of results. Our findings provide support for the convergent and concurrent validity of these two measures and suggest that the single-item Contemplation Ladder may be a practical alternative to the URICA in certain situations.

Adult↗

PubMed2004

Discriminative stimulus effects of gamma-hydroxybutyrate in pigeons: role of diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors.

gamma-Hydroxybutyrate (GHB) is an emerging drug of abuse with multiple mechanisms of action. This study is part of an effort to examine the role of GHB, GABA(A), and GABA(B) receptors in the discriminative stimulus (DS) effects of GHB. In pigeons trained to discriminate 100 mg/kg GHB from saline, GHB and its precursors gamma-butyrolactone and 1,4-butanediol produced 80 to 100% GHB-appropriate responding, whereas other compounds such as morphine, naltrexone, cocaine, and haloperidol produced no more than 34%. Compounds interacting with GABA receptors produced different maximal levels of GHB-appropriate responding. For example, the GABA(A) agonist muscimol produced 3%; the GABA(A)-positive modulators diazepam, pentobarbital, and ethanol, and the GABA(B) agonist baclofen produced levels ranging from 54 to 73%; and the benzodiazepine antagonist flumazenil and inverse agonist Ro 15-4513 (ethyl 8-azido-6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-alpha]-[1,4]-benzodiazepine-3-carboxylate) both produced 96%. The putative GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) produced 70% GHB-appropriate responding. The GABA(B) antagonist (3-aminopropyl)(diethoxymethyl)phosphinic acid (CGP 35348) completely blocked the GHB-like DS effects of NCS-382 and baclofen at a dose of 56 mg/kg. CGP 35348 also blocked the DS effects of GHB, but incompletely and only at a dose of 560 mg/kg. Together, these results are consistent with a role for diazepam-sensitive and -insensitive GABA(A) and GABA(B) receptors in the DS effects of GHB. Together with previous findings, the present results suggest that diazepam-insensitive GABA(A) receptors are more prominently involved in the DS effects of GHB in pigeons than in rats, whereas GABA(B) receptors are less prominently involved. Exploring the role of GHB receptors with NCS-382 is hampered by its GABA(B) receptor-mediated, GHB-like agonist activity.

Animals↗

PubMed2004

Improving contingency management programs for addiction.

Contingency management interventions effectively reduce or eliminate some individuals' problem substance use. Typically, those who do not benefit never experience the reward or planned contingency available through the intervention because they never produce the behavior (often abstinence) on which the reward is contingent. With two analog studies, we examine whether the effectiveness contingency management interventions improves when contingencies are arranged in ways that improve the likelihood of all participants experiencing the available reward. Participants were smokers not planning to quit. In Study 1, smokers were paid 0, 1, 3, 10, or 30 dollars each day for 5 days for delivery of breath carbon monoxide (CO) levels either < or =4 ppm or below half the median of their baseline levels. Higher payment amounts and the easier target criterion resulted in a higher likelihood of participants meeting criterion. Once participants met the 4 ppm criterion, however, they often maintained this behavior even in the absence of payments for reduced breath CO levels. An ineffective contingency management system was made effective based on these results. Study 2 examined the effectiveness of percentile schedules at reducing breath CO levels. Percentile schedules shaped lower breath CO levels. The effectiveness of percentile schedules in shaping abstinence was tested in treatment seekers, and percentile schedules were found to be effective at shaping abstinence.

Behavior Therapy↗

PubMed2004

Seedling and adult plant resistance to Sitobion avenae (Hemiptera: Aphididae) in Triticum monococcum (Poaceae), an ancestor of wheat.

Cereal aphids are important pests of wheat, Triticum aestivum L. and Triticum durum Desf. Crop resistance is a desirable method for managing cereal aphids in central North America, where the dominant crop, spring-sown wheat, has a low value per unit area. A diploid ancestor of wheat, Triticum monococcum L., is reported to be partially resistant to Sitobion avenae (Fabricius), the most damaging cereal aphid in the region. To identify potential sources of resistance, 42 accessions of T. monococcum and three cultivated wheats were infested with aphids, seedlings for six days and adult plants for 21 days. Overall resistance was estimated by the biomass loss of foliage and spikes in relation to uninfested control plants. Antibiosis was estimated by the gain in biomass of aphids during infestation, and tolerance was estimated as a biomass conversion ratio, overall resistance divided by antibiosis. A few T. monococcum accessions exhibited partial resistance. No relationship was found between seedling and adult plant resistance: the former exhibited primarily antibiosis and the latter primarily tolerance. Two accessions with antibiosis reduced aphid biomass by 60% compared with commercial wheats. Tolerance was correlated with growth potential, and was useful only in accessions with high growth potential. Four accessions exhibited tolerance levels at least 30% greater than commercial wheats. Highly susceptible accessions also were identified, which would be useful for investigating the inheritance of antibiosis and tolerance.

Animals↗

PubMed2004

An interspersed refuge for Sitodiplosis mosellana (Diptera: Cecidomyiidae) and a biocontrol agent Macroglenes penetrans (Hymenoptera: Pteromalidae) to manage crop resistance in wheat.

An interspersed refuge of susceptible plants in a resistant, spring-sown wheat crop was tested as a strategy to protect crop resistance against evolution of virulence by the wheat midge Sitodiplosis mosellana (Géhin), and also to conserve a biocontrol agent Macroglenes penetrans(Kirby). Eight replicated field experiments were conducted using seed mixtures of 0, 5, 10, 15 and 100% or 0, 5 and 100% susceptible wheat with an agronomically similar wheat expressing the antibiotic resistance gene Sm1. The frequencies of eggs, mature larvae and parasitized larvae in susceptible and resistant wheat spikes, and midge-affected seeds in the harvest, were recorded for each plot. In susceptible wheat, insect densities and seed damage were typical of those in commercial wheat. In resistant wheat, few larvae completed development, 2% or less compared with about 80% in susceptible wheat, when larvae were sampled at maturity. This resistant wheat also deterred midge oviposition, reducing egg densities by 65% compared with susceptible wheat. The wheat midge and its parasitoid oviposited throughout the plots, and parasitism was density independent. The densities of mature midge larvae and parasitoids were in proportion to the size of the refuge. A 5% susceptible refuge produced about 41 mature larvae for each mature larva from the resistant wheat, and provided effective control of damage. An interspersed refuge of susceptible plants in resistant wheat is a promising strategy for sustaining resistance conferred by Sm1 and biocontrol of the wheat midge.

Animals↗

PubMed2004

Sex ratios of Sitodiplosis mosellana (Diptera: Cecidomyiidae): implications for pest management in wheat (Poaceae).

Sex ratios of populations of the wheat midge Sitodiplosis mosellana Gehin, developing on wheat Triticum aestivum L., were determined at reproduction, adult emergence, and dispersal. The patterns of sex ratio through the life cycle of S. mosellana result from: (i) a genetic mechanism that causes all or nearly all of the progeny of individual females to be a single sex, with an overall sex ratio that is slightly biased at 54-57% females; (ii) a differential mortality during diapause that increases the sex ratio to 60-65% females; (iii) mating which occurs near the emergence site followed by female dispersal which causes the post-dispersal sex ratio to rise to nearly 100% females; and (iv) oviposition which spreads eggs among different plants and assures that the next generation has a local sex ratio close to the population average. These changes in sex ratio through the life cycle have implications for using crop resistance or pheromones to manage S. mosellana, because mating takes place quickly near emergence sites, and because mated females but not males disperse from emergence sites to oviposition sites. Crop refuges used to protect resistance genes against the evolution of virulence by S. mosellana must be interspersed to prevent assortative mating that would occur in separate blocks of resistant and susceptible plants. Monitoring or mating disruption using a pheromone would be ineffective when wheat is grown in rotation with a non-host crop.

Agriculture↗

PubMed2003

Effects of gamma-hydroxybutyrate (GHB) on schedule-controlled responding in rats: role of GHB and GABAB receptors.

Gamma-hydroxybutyrate (GHB), a metabolite of gamma-aminobutyric acid (GABA), is an increasingly popular drug of abuse and was recently approved for the treatment of narcolepsy (Xyrem). GHB and GABA receptors have been implicated in mediating effects of GHB; however, the relative importance of each of these receptors is unclear. This study evaluated the effects of selective antagonists in combination with GHB and related compounds on schedule-controlled responding. Eight male Sprague-Dawley rats responded under a fixed-ratio schedule of food presentation. Cumulative dose-effect curves were generated and ED50 values calculated to evaluate the relative potency at decreasing responding. The rank-order potency was as follows: diazepam = baclofen > gamma-butyrolactone (GBL) > 1,4-butanediol (1,4-BDL) = GHB. All compounds decreased responding 20 min after administration. The duration of action of diazepam, GHB, and GBL was shorter than that of 1,4-BDL and baclofen. p-3-Aminopropyl-p-diethoxymethyl phosphinic acid (CGP 35348) antagonized the rate-decreasing effects of baclofen and not GHB; flumazenil antagonized the effects of diazepam and not GHB. The GHB receptor antagonist (2E)-(5-hydroxy-5,7,8,9-tetrahydro-6H-benzo[a][7]annulen-6-ylidene ethanoic acid (NCS-382) did not attenuate the rate-decreasing effects of GHB, baclofen, or diazepam; larger doses of NCS-382 further decreased rate of responding when given in combination with each of these compounds. These studies show that GBL, 1,4-BDL, and GHB differ significantly in potency and duration of action. The ability of CGP 35348 to antagonize the rate-decreasing effects of baclofen may be limited by the involvement of multiple GABAB receptor subtypes and the lack of antagonism of GHB by NCS-382 may be due to its own GHB-like effects.

Anesthetics, Intravenous↗