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PubMed2003

Estimates of genetic parameters and selection strategies to improve the economic efficiency of postweaning growth in lambs.

The objectives of this study were to estimate (co)variance components for growth and feed efficiency measures, and to compare selection strategies to improve economic efficiency of gain. Variance components for pre- and postweaning growth, body weight, and measures of feed efficiency were estimated from data collected on 1,047 Targhee lambs over 7 yr. Approximately 21 d after weaning, lambs were group-fed for 4 wk, with ad libitum access to a diet of 37% whole barley grain and 63% pelleted alfalfa hay. Lambs were then individually fed for 6 wk. Lambs were then returned to group feeding for another 4-wk period. The mean feed conversion ratio (gain/intake) for the individual feeding period was 0.11. Mean postweaning ADG for the total 14-wk feeding period was 0.26 kg. (Co)variance components were estimated from single- and two-trait animal models using REML. The selection strategies compared included direct selection, index selection, and restricted index selection. Estimates of (co)variances derived from single- and two-trait models were similar, except for mid-test body weight. Preweaning growth had a low heritability estimate (0.03 +/- 0.04) compared with postweaning growth measures (0.25 to 0.39), but all measures of growth were highly correlated (r2 > 0.98). Heritability estimates of measures of gain efficiency were variable (total feed intake = 0.39; feed conversion ratio = 0.26; residual feed intake = 0.26). Total feed intake was strongly correlated genetically with feed conversion ratio (0.79) and residual feed intake (0.77). The estimate of genetic correlation between feed conversion ratio and residual feed intake was low (0.23). Comparison of selection strategies showed the superiority of index selection (ADG, total feed, body weight) for economic improvement compared with other strategies. Economic response to direct selection for ADG was at least twice that for direct selection for feed conversion ratio or against total feed intake, and that for restricted indices (selecting against residual feed, while holding body weight and/or gain constant). Selection for ADG may be a practical approach for indirectly improving efficiency of gain in lambs.

Analysis of Variance↗
PubMed2003

Evaluation of strategies for selection for lean growth rate in pigs.

Lean growth rate (LGR) in pigs is a nonlinear biological function of growth rate and lean quantity. According to animal breeding theory, genetic progress for LGR is maximized with selection on a linear index of its component traits, but selection on direct EBV for LGR is also common. In this study, the performance of five criteria for selection on estimated LGR in pigs was evaluated through simulation over five generations: linear indexes of multiple-trait EBV of component traits with or without updating index weights in each generation; a nonlinear index of multiple-trait EBV of component traits; and direct selection on EBV for LGR from a single-trait model or a multiple-trait model that included LGR and component traits. The nonlinear index yielded the highest response in LGR in Generation 5, but the linear index with updating performed almost as well. Not updating weights for the linear index reduced response in LGR by 1.1% in Generation 5 (P < 0.05). Direct selection on single-trait EBV for LGR yielded the lowest responses in Generation 5. Direct selection on EBV for LGR from a multiple-trait animal model yielded a 3.1% greater response in LGR in Generation 5 than direct selection on EBV for LGR based on a single-trait animal model (P < 0.05), but yielded a 1.9% lower response than the nonlinear index. Although differences in response in LGR were limited, alternative selection criteria resulted in substantially different responses in component traits. Linear index selection for LGR placed more emphasis on lean quantity, whereas direct selection for LGR emphasized growth rate. Based on the relative changes in the responses in LGR, selection for estimated LGR based on a nonlinear index or a linear index with updating is recommended for use in the swine industry.

Adipose Tissue↗
PubMed1987

Divergent selection for postweaning feed conversion in beef cattle: predicted response based on an index of feed intake and gain vs fee: gain ratio.

As part of a divergent selection experiment (high vs low feed conversion) designed to obtain realized genetic parameter estimates for postweaning feed conversion, 35 Angus bull calves were selected each year from 1979 through 1983 to be fed in a 140-d postweaning performance test. From these 35 individually-fed bulls, the three most efficient and three least efficient (in terms of kilograms of total digestible nutrients required per kilogram of gain) were selected each year to each be mated to approximately 20 purebred Angus cows in a test herd. In the last 2 yr of the experiment, feed:gain ratios were adjusted for differences in maintenance requirements before selection. An alternative to selection based on feed/gain or adjusted feed/gain would have been to select on an index of feed intake and gain (Index3 = -1.0 feed intake + 3.87 gain) where feed intake was either unadjusted or adjusted (AdjIndex3) for differences in maintenance requirements. Residual correlations (year effects removed) among the four selection critera were large ([r[ greater than or equal to .76; P less than .01) as were correlations among ranks of the bulls based on the four selection criteria ([r[ greater than or equal to .75). Predicted genetic change for fee:gain ratio in both the high and low directions was greatest when selection was based on feed:gain ratio or Index3. Genetic changes expected to result from selection for feed:gain ratio or Index3 were similar, as were genetic changes expected due to selection for adjusted feed:gain ratio or AdjIndex3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗
PubMed2002

Superiority of QTL-assisted selection in dairy cattle breeding schemes.

The superiority of selection schemes employing information about a known quantitative trait locus (QTL) over conventional schemes is examined for dairy cattle breeding schemes. Stochastic simulation of a dairy cattle population with selection practices, structures, and parameters similar to the US Holstein population was implemented. Additive genetic effects were estimated by an animal model. Two schemes were compared: a QTL-assisted selection scheme in which the genotype of a known QTL was accounted for in the animal model as a fixed factor, and a QTL-free selection scheme in which the QTL was simulated but was not fit separately in the animal model. Under the QTL-assisted selection scheme, all animals in the mixed model were assumed to be genotyped for the QTL. The effect of using QTL information on the genetic response, the frequency of the favorable QTL allele, and the accuracy of evaluation were examined. Moreover, the effect was studied in four distinct paths of selection: active sires, proven young bulls, bull dams, and first-lactation cows. Average superiority values of 4.6, 7.6, 11.7, and 1.1% for genetic response were observed over 16 yr of selection for active sires, young bulls, bull dams, and first-lactation cows, respectively. Frequency of the favorable QTL allele changed faster in bull dams than males, and was the slowest in first-lactation cows. Finally, accuracy of evaluation under the QTL-assisted selection scheme was higher than under the QTL-free selection scheme. Young bulls ofthe QTL-assisted selection scheme on average had 0.049 higher accuracy, and first-lactation cows had on average 0.185 higher accuracy than corresponding animals of the QTL-free selection scheme.

Animals↗
PubMed1996

Long-term selection for body weight in Japanese quail under different environments.

Long-term selection was conducted for high 4-wk BW in Japanese quail under different selection environments to investigate selection limits and to determine whether genetic parameters for growth are similar to those in chickens. Quail lines were selected under an adequate 28% CP diet (P line) and under a low 20% CP diet (T line). Mean realized heritabilities ranged from 0.32 (T line) to 0.49 (P line) during the first 10 generations. Although genetic variation remained following 97 generations of selection, realized heritabilities obtained agreed with theoretical predictions of loss of additive genetic variability with continuous selection. Similarity of heritability estimates indicates that Japanese quail are an excellent model for genetic studies of growth in meat-type chickens. Positive relationships accompanying selection for high 4-wk BW were increases in adult BW, age at first egg, and egg weight. Negative relationships were decreases in percentage fertility and hatchability, and egg production. Increased growth rate in selected lines was accompanied by an increase in feed and water intake, and by improvement in feed efficiency. Feed efficiency differences appeared to be important only immediately following hatch, whereas feed intake differences were present from 0 to 4 wk. Evidence of major physiological changes accompanying selection for growth were not observed. However, changes were observed in increased "resource allocations" to supply organs, during late embryonic stages and the 1st wk posthatch. Carcass composition was similar between unselected and selected lines except for higher fat and lower moisture levels in selected lines.

Animals↗
PubMed2002

Forward, relaxed, and reverse selection for reduced and enhanced sensitivity to ethanol's locomotor stimulant effects in mice.

BACKGROUND: Rarely have trait markers for alcoholism risk been identified. However, relative sensitivity to the arousing effects of ethanol and sensitivity to ethanol's sedative effects have been distinguished as potentially valuable behavioral risk factors. Both traits are genetically influenced and have been modeled in mice by measuring sensitivity to ethanol-induced locomotor stimulation and hypnosis. Reverse selection was performed to examine the hypothesis that forward selection for differential sensitivity to ethanol's locomotor stimulant effects resulted in homozygous fixation of selection trait-relevant alleles and to test the hypothesis that common genes influence ethanol's stimulant and sedative effects. METHODS: Bidirectional selective breeding was completed for enhanced (FAST mice) and reduced (SLOW mice) sensitivity to ethanol's locomotor stimulant effects. Selection was terminated (relaxed), and the lines were tested to detect genetic drift. Reverse selection for enhanced sensitivity to ethanol-induced stimulation in SLOW mice and reduced sensitivity in FAST mice was performed for 16 generations. Forward and reverse selected lines were tested for sensitivity to ethanol's sedative effects by measuring duration of ethanol-induced loss of righting reflex. RESULTS: Differential sensitivity to the sedative effects of ethanol emerged with selection for differential ethanol stimulation, indicating a common genetic influence on these traits. SLOW mice developed greater sensitivity to ethanol's sedative effects relative to FAST mice. Reverse selection, never before reported for a pharmacogenetic trait, was effective in eliminating most of the difference in stimulant sensitivity between the FAST and SLOW lines and also eliminated the difference in loss of righting reflex duration. CONCLUSIONS: Residual heterozygosity persisted at trait-relevant loci even at the selection plateau, possibly due to heterosis, natural selection favoring heterozygosity, or epistatic phenomena involving differences in the sets of genes regulating the high- versus low-sensitivity traits. They also suggest that some common genes influence sensitivity to ethanol's locomotor stimulant and sedative effects.

Alcohol Drinking↗
PubMed2005

Correlational selection leads to genetic integration of body size and an attractive plumage trait in dark-eyed juncos.

When a trait's effect on fitness depends on its interaction with other traits, the resultant selection is correlational and may lead to the integration of functionally related traits. In relation to sexual selection, when an ornamental trait interacts with phenotypic quality to determine mating success, correlational sexual selection should generate genetic correlations between the ornament and quality, leading to the evolution of honest signals. Despite its potential importance in the evolution of signal honesty, correlational sexual selection has rarely been measured in natural populations. In the dark-eyed junco (Junco hyemalis), males with experimentally elevated values of a plumage trait (whiteness in the tail or "tail white") are more attractive to females and dominant in aggressive encounters over resources. We used restricted maximum-likelihood analysis of a long-term dataset to measure the heritability of tail white and two components of body size (wing length and tail length), as well as genetic correlations between pairs of these traits. We then used multiple regression to assess directional, quadratic, and correlational selection as they acted on tail white and body size via four components of lifetime fitness (juvenile and adult survival, mating success, and fecundity). We found a positive genetic correlation between tail white and body size (as measured by wing length), which indicates past correlational selection. Correlational selection, which was largely due to sexual selection on males, was also found to be currently acting on the same pair of traits. Larger males with whiter tails sired young with more females, most likely due to a combination of female choice, which favors males with whiter tails, and male-male competition, which favors both tail white and larger body size. To our knowledge, this is the first study to show both genetic correlations between sexually selected traits and currently acting correlational sexual selection, and we suggest that correlational sexual selection frequently may be an important mechanism for maintaining the honesty of sexual signals.

Animals↗
PubMed1986

[The role of natural selection in evolution].

To evaluate properly a role of natural selection, its effect should be considered in relation to different phases of the evolutionary cycle postulated earlier by the author. At the first stage of the cycle natural selection is directed towards organism's persistence to detrimental external factors and leads to an increased fitness (that is viability and fecundity) in every generation. At the next stage of the cycle natural selection occurs under conditions of intraspecific competition and is directed towards a more efficient utilization of food resources. At this stage natural selection leads to formation and divergence of intraspecific races and is carried out by "single" selection actions occurring now and then and consisting of the survival of rare mutants with an altered ecological potential. Such a strict selection for certain mutants occurs again during the periods of acute competition for food, the selected mutants being characterized by a decrease of fitness, the latter to have been restored by means of the "ordinary" selection within the intervals between crises. According to the model suggested, homozygotes for "detrimental" recessive alleles could be selected in diploids, as the mutants mentioned with altered ecological potential. At the end of the cycle, there is a kind of selection for hybrids in which ecological potential of specialized intraspecific races is combined. The genetic drift is considered as an inevitable consequence of the postulated mechanism of natural selection.

Alleles↗
PubMed1982

[Effectiveness of selection for thorax length in model Drosophila populations in chemical mutagen exposure].

Artificial selection for increasing and decreasing Drosophila thorax length was carried out over 20 generations. Chemical mutagen, dimethylsulfate (DMS) was regularly applied to enhance genetic variation in selected lines. It was determined that under the influence of mutagen the efficiency of selection for decreasing thorax length was much higher, while selection course for increasing thorax length was not affected significantly. Regression coefficient of responses to selection, general for males and females, was equal to b = -0.035 +/- 0.004 for lines of negative direction of selection when the mutagen was applied and -b = -0.023 +/- 0.004 without mutagenesis; for lines of positive direction b = 0.026 +/- 0.005 and b = 0.024 +/- 0.005. Fitness component variation by artificial selection was studied. A complex correlation was detected between direction of selection, the shift value of model quantitative character and fitness component variation by selection. The main factor stimulating a sharp drop of average fitness of lines appeared to be the influence of directional artificial selection. The regular treatment by a moderate dose of the mutagen did not affect markedly the average fitness variation of selected lines.

Animals↗
PubMed1995

[Regulatory selection as an alternative to the neutrality theory].

Regulatory selection is the most typical mode of natural selection responsible for the optimization of the regulatory systems of an organism. In addition to regulatory selection, stringent selection of pleiotropic mutants or recombinant forms with altered ecological potential operates in successful species during vertical evolution. Regulatory selection stabilizes alterations in the ecological potential, acting at intervals between larger regulatory genome alterations occurring at the boundaries between evolutionary phases. Fisher's adaptive model can be applied to regulatory selection. At each separate evolutionary phase, the selection coefficients in selected mutants decline gradually. At the final stage of the evolutionary phase, mutations with a minor selective advantage are selected. Hence, regulatory selection may be regarded as an alternative to the neutral evolution theory.

Animals↗
PubMed1996

[Selection in vivo in cell populations of rat RA-23 rhabdomyosarcoma at the trait "frequency of cells with bridges"].

Selection in vivo of cell clones of rat transplantable organospecific rhabdomyosarcoma RA-23 for increased and decreased frequencies of cells with chromosomal bridges (FCB) was performed. The initial average FCB in clones was 0.8% at a range of variation of from 0 to 3.0%. Selection for an increase, as well as for a decrease, in the FCB in RA-23 clones was effective. After one step of selection for an increase in the FCB, the average FCB increased to 3.0%. Thereafter, selection for an increase in the FCB was impracticable due to loss of transplantability in cell populations in which the FCB exceeded 5.0%. Over five steps of selection for a decrease in the FCB, the average FCB significantly decreased to 0.3% (P < 0.001). The heritability coefficient h2 of the trait FCB upon selection ranged from 0.25 to 0.30. The high and low FCBs attained by selection correlated with the index "frequency of cells with micronuclei." The population of RA-23 cells after selection for a decrease in the FCB differed from the population of cells of the original RA-23 strain by significantly lower karyotypic heterogeneity. The values of h2 obtained upon selection for the FCB and the effectiveness of selection for an increase, as well as for a decrease, in the FCB show that, with selection at the trait "frequency of cells with bridges," which characterizes the stability of the karyotype, existing cell strains can be subjected to karyotypic stabilization or destabilization.

Animals↗
PubMed1997

Interpreting the term selection bias in medical research.

The issue of selection bias is often raised in the critical appraisal of medical studies, but it is often poorly defined and misunderstood. This paper, describes three common patterns of use of the term selection bias and their effects on study results. The three ways in which selection bias is used are related to 1) selection of representative subjects, 2) selection of subjects to exposures, and 3) selection of subjects at outcome. Avoidance of bias in the first of these issues, selection of representative subjects, enhances the ability to generalize a study's results. The other two uses of selection bias relate to the internal validity of studies. The selection of subjects to exposures without randomization in observational studies can distort results because of confounding variables. The selection of study subjects at outcome in case-control and cross-sectional studies can distort study findings if selection into the study is distorted according to exposure status. Readers of medical studies should understand the different implications of these uses to improve their critical evaluation of studies. Writers and discussants should be aware of these differences and provide clarifying details when they use the term.

Case-Control Studies↗
PubMed1998

Mutation and selection within the individual.

Selection within the individual may have played a critical and creative role in evolution, boosting the survival chances of mutations beneficial to the cell and the individual, hindering the spread of deleterious mutations, and reducing the genetic load imposed on the population. We review the literature and present new results to describe the effects of cell-lineage selection on the rate and fixation probability of new mutations. Cell-lineage selection can alter these quantities by several orders of magnitude. Cell-lineage selection is especially important in the case of rare recessive mutations, which are hidden from selection at the individual level but may be exposed to selection at cellular level. Because selection within the individual acts as a sieve eliminating deleterious mutations and increasing the frequency of beneficial ones, mutations observed among progeny will have been pre-selected and are more likely to increase cell proliferation than would randomly generated mutations. Although many authors have focused on the potential conflict between selection at the cellular and individual levels, it must be much more common that the two levels act concordantly. When selection at the cell and individual levels act in a cooperative manner, increased rather than decreased opportunity for germline selection will be favored by evolution.

Animals↗
PubMed2000

Degree of ERK activation influences both positive and negative thymocyte selection.

Considerable evidence suggests that the ERK pathway is required for positive but not negative thymocyte selection. Here, we report that ERK is highly activated in double-positive (DP) thymocytes expressing an MHC class I-restricted TCR (P14) in response to negatively selecting conditions, whereas ligands that trigger positive selection induced weaker ERK activation. Biochemical evidence also shows that death by neglect is associated with a further reduction in ERK activation. These findings are consistent with the affinity / avidity model of thymocyte selection. To further examine the role of ERK in negative selection we used the MEK-1 inhitibor, PD98059, a specific pharmacological inhibitor of the ERK pathway. Biochemical data demonstrated a reduction of ERK activity by PD98059 in the presence of the negatively selecting ligand. Analysis of P14 TCR-transgenic fetal thymic lobes cultured with PD98059 under negatively selecting conditions showed impaired clonal deletion of DP thymocytes and a concomitant increase in positive selection of functional mature, TCR(hi) transgenic T cells. This demonstrates that altering ERK activity switched negative to positive selection. Contrary to previous reports that show an exclusive role for ERK signaling in positive selection, our data demonstrate that negative selection is also sensitive to the degree of ERK activation.

Animals↗
PubMed1976

Selective breeding of mice for antibody responsiveness to flagellar and somatic antigens of salmonellae.

Selective breeding has been performed in mice for their high or low antibody responsiveness to Salmonella antigens (Ag). Two noncross-reacting Salmonellae (S. typhimurium and S. oranienburg) have been alternately used to immunize successive generations in order to avoid interference of maternally transmitted antibody. Both Salmonellae carry two independent antigens: flagellar (f) and somatic (s). Two two-way selections were carried out: one for agglutinin response to fAg and the other for agglutinin response to sAg (Selection Ags). The agglutinin response to the other independent Ag was also measured (Associated Ags). The phenotypic character chosen for selection is the maximal agglutinin titer in response to optimal immunization. In both selections, high and low responder lines diverged progressively. There was a 27-fold interline difference in the F13 generation of selection for fAg response and a 38-fold one in the F11 generation of selection for sAg response. This divergence and the continuous distribution of phenotypes in the foundation population indicate that the quantitative character investigated is subject to polygenic regulation. The realized heritability (h2) of the character, measured from the interline divergence, was 0.18 +/- 0.06 in both f and s selections. This means that about 20% of the phenotypic variance of the foundation population is additive. The modification of immune responsiveness to the selection Ag produced by selective breeding was accompanied by a parallel and equivalent effect on immune responsiveness to the noncross-reacting Associated Ag. This effect is therefore entirely nonspecific. A small but definite sex effect in favor of female antibody responsiveness was demonstrated. The results are discussed in comparison with other selection experiments made in mice for quantitative antibody response to other antigens.

Animals↗
PubMed1985

Selection for different growth parameters in laboratory mice and its correlated effects on body composition and organ weights.

Body composition and organ weights were determined in male mice sampled from 4 different lines of a selection experiment: DU-6P (selected for high protein amount), DU-6 (selected for high body weight), DU-6 + LB (selected for an index combining body weight and endurance fitness) and DU-K (unselected control line). Selection was carried out under the conditions of ad libitum feeding and standardization of litter size at birth. In all 3 selection lines a significant direct selection response was shown. While fat in lines DU-6P and DU-6 + LB remained normal, it increased after selection for body weight (DU-6) significantly. Up to generation 13 the average increase of fat was 0.32% per generation. Investigations on 28 to 80 days old mice showed, that males of this line were fatter before, at and after the age of selection (42 days). After 9 generations the body weight of selected mice was significantly increased by 23 to 29%. The absolute organ weights of hearts, livers and kidneys were also significantly higher, while the relative weights of hearts and kidneys decreased. The relative liver weights were in the selected lines higher, but only the difference DU-6 vs. DU-K was significant.

Animals↗
PubMedDate not supplied

Evaluation of ICSI-selected epididymal sperm samples of obstructive azoospermic males by the CKIA system.

The objective of this study was to evaluate nuclear normality in intracytoplasmic sperm injection (ICSI)-selected epididymal sperm from obstructive azoospermic (OA) patients. We evaluated whether the selection criteria used in routine ICSI (morphology and motility at a magnification of 400x) is adequate for selecting "normal" sperm from epididymal samples. Surgically retrieved spermatozoa from the caput epididymis of 15 OA patients and ejaculated sperm samples from 9 normospermic donors were evaluated with a DNA-specific stain (Feulgen) and in combination with the computerized karyometric image analysis (CKIA) system. Original (unselected) samples and ICSI-selected sperm were compared in donor and patient samples. In the original fraction, a larger variation in almost all measured parameters was found in epididymal sperm than in ejaculated sperm. After sperm selection, the morphometry was comparable between epididymal and ejaculated sperm. However, for those parameters related to the DNA stainability and chromatin texture (nuclear condensation), significant differences between patients and donors were observed. This result suggests that the size and form of the sperm do not necessarily hold similar internal structures. Thus, the frequency of "normal" sperm significantly increased after ICSI selection, but the improvement was more marked in donor than in OA patients' samples. In conclusion, at least a twofold increase in the number of normal spermatozoa was achieved after ICSI selection. The heterogeneity in the stainability and chromatin condensation of epididymal samples from OA patients indicates that some of the selected spermatozoa have a hypocondensed or hypercondensed chromatin. Even in the best of donor cases, no more than 55% of the selected sperm scored normal with CKIA, indicating that the present routine ICSI selection criteria are not sufficient for selecting normal condensed nuclei.

Ejaculation↗
PubMed1988

Site-selective serotonin agonists as discriminative stimuli.

Various direct- and indirect-acting serotonin (5-HT) agonists serve as training drugs in tests of stimulus control of behavior; such agents include: 5-hydroxytryptophan, 5-methoxy-N,N-dimethyltryptamine, and fenfluramine. However, with the recent discovery of multiple populations of central 5-HT binding sites, the concept of site-selective serotonergic agents needs to be addressed. Certain 4-substituted 1-(2,5-dimethoxyphenyl)-2-aminopropanes such as DOM (4-methyl), DOB (4-bromo), and DOI (4-iodo) appear to be 5-HT2-selective agonists and serve as effective training drugs in rats. Stimulus generalization occurs among these agents regardless of which is used as the training drug, although stimulus generalization does not occur with 5-HT1A-selective agonists [e.g., 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH DPAT)] or with 5-HT1B-selective agonists [e.g., 1-(3-trifluoromethylphenyl)piperazine (TFMPP)]. 8-OH DPAT and TFMPP also serve as training drugs; the 8-OH DPAT-stimulus generalizes to other 5-HT1A agonists, but not to 5-HT1B or 5-HT2 agonists, whereas the TFMPP-stimulus generalizes to other 5-HT1B agonists, but not to 5-HT1A or 5-HT2 agonists. Classical serotonin antagonists, most of which are rather selective for 5-HT2 sites, and 5-HT2-selective antagonists are able to block the stimulus effects of DOM, DOB, and DOI, but not those of 8-OH DPAT or TFMPP. The results of such studies reveal that, in rats, site-selective 5-HT agonists produce stimulus effects that are also selective; although generalization may occur with nonselective 5-HT agonists, animals trained to discriminate site-selective 5-HT agonists apparently do not recognize other 5-HT agonists that are selective for a different site. Animals trained to discriminate such agents from saline might be useful for the identification and/or investigation of novel site-selective agonists and antagonists (for example, the 8-OH DPAT-stimulus generalizes to members of a new class of anxiolytics that display high affinity for 5-HT1A binding sites), and might also aid in the overall understanding of central serotonergic mechanisms.

Animals↗