The effects of lysergic acid diethylamide on copulatory behaviour in the female rat.

The actions of lysergic acid diethylamide (LSD) on a serotonin- and dopamine-dependent functional test, lordotic behaviour in female rats, and other behaviours were investigated. Increasing doses of LSD inhibited the display of lordosis in increasing numbers of females. Also locomotor activity and habituation of a startle reaction were impaired. Pretreatment with a large single dose of p-chlorophenylalanine, which by itself induced lordosis in all subjects tested, caused an enhancement of the LSD effect, prolonging its duration. When p-chlorophenylalanine was replaced by α-methyl-p-tyrosine, all females showed lordosis by this treatment alone, while a combination with LSD had a significantly briefer effect than this dose of LSD alone. Repeated administration of smaller doses of p-chlorophenylalanine did not by itself alter the response level in a group of females, and together with LSD the effect was of a shorter duration than after the single dose of p-chlorophenylalanine. Inhibition of lordosis was not related to impairment of locomotor capacity. These differential effects after pretreatment with the synthesis inhibitors in addition to other data discussed indicate that certain functional effects of LSD could be related to increased serotonin activity.     

A pavlovian procedure for improving sexual performance of noncopulating male rats

Previous research has shown that Pavlovian conditioning, based on unconsummated arousal, can increase copulatory rate in laboratory rats. This investigation tested whether a similar procedure could improve the performance of males that initially fail to copulate successfully. Male rats that did not reach ejaculation with a receptive female on a pretest were randomly assigned to one of two groups: CS-US paired or CS-US unpaired. The CS consisted of a period of placement in a running wheel which allowed measurement of incidental activity. The US was (arousing) exposure to a female separated from the male by a wire mesh screen. The CS immediately preceded the US for the paired group but the two were unpaired for the control group. Following conditioning, CS and No-CS tests were given, with both copulation and activity measures taken. Subjects in the paired group were significantly more likely to achieve ejaculation on the CS test than those in the control group, and they were also more active during the test. In contrast, differences on the No-CS test were not significant, consistent with expectations from a Pavlovian explanation. These data show the efficacy of Pavlovian procedures in improving sexual performance, with a possible application to increase arousal to selected cues for human subjects, e.g., some individuals with erectile dysfunction.This research was supported by a grant from the National Science and Engineering Research Council of Canada.     

Comparative studies of four Drosophila P-insertion mutants with memory defects

Studies of conditioned reflex courtship suppression in mutant Drosophila males in two tests – a memory retention test (with a virgin female) and a repeat training test (with a fertilized female) – yielded experimental support for a previously suggested physiological model of the acquisition of this reflex. Mutations altered both types of conditioned association suggested in the model, i.e., the association between the conditioned and unconditioned stimuli (lat, rut, dnc, amn, and P153) and the association between the conditioned stimulus and the aversive motivational system mediating the action of the unconditioned stimulus (P171). A third category of mutants appeared to have a disturbance to the function of the aversive motivational system (P95 and P124).     

The ability of Drosophila mutants with defects in the central complex and mushroom bodies to learn and form memories

One of the most important questions in the genetics of behavior is that of studies of the mechanisms of learning and memory. A convenient system for this is provided by Drosophila melanogaster, in which a whole series of mutations affecting the formation of different types of memory and learning have been obtained. The brain formations involved in these processes have been studied in parallel. Attention is currently focused on two main structures: the central complex and the mushroom bodies. These mediate the integration and storage of information accumulating during the process of learning. Mutants with defects in individual parts of the central complex and mushroom bodies have been obtained. Mutants simultaneously affecting the operation, development, or structure of the central part of the cerebral neural ganglion and the ability to learn and form memory traces are of particular interest. We have evaluated the learning ability of mutants with defects in the central complex (cex ^KS181 and ccb ^KS127) and mutants with defects in the mushroom bodies (mud ¹, mbm ¹, and cxb ^N71), using a method based on the conditioned reflex suppression of courtship. Memory defects were seen in cex ^KS181 and mud ¹ mutants.     

Minority mating advantage of certain eye color mutants ofDrosophila melanogaster. IV. Female discrimination among three genotypes

It was our purpose to examine how the courtship sequence by three eye color types of males inDrosophila melanogaster might affect the experience of females in such a way as to influence mating success. Flies were mutants for a pair of alleles at thebrown locus (bw andbw ⁷⁵; 104.5 on chromosome 2) combined withscarlet (st; 44.0 on chromosome 3). Mutant red-eyed (R), orange-eyed (O), and white-eyed (W) flies were tested, mature virgin females individually in the presence of six males, either three each of two eye color types or two each of three types. About 12% of the females displayed a low threshold and mated to the first male that courted in less than 5 min. For these females and for those with a higher threshold when courted by one type of male only, R males were twice as successful as O and about four times as successful as W. For trials in which two male types courted, females tended to accept the type that was not the first to court in 62.5% of the trials with a 33 ratio of males and in 70% of the trials with a 222 ratio but one type of male not courting. When all three types of males courted at the latter ratio, females tended to discriminate against both the first type to court and the joint combination of first with second type to court, tending to mate with the third type in 47% of the trials. There was no significant association between either the second male or the second type of male to court and the type that mated. Evidence is presented that the visual component of courtship is important to persistence and efficiency but less important to initiation of courtship. The time to mating (female acceptance) is longer with increase in the number of male types courting. These results and some arguments by other authors trying to account for negative results using the same mutants are discussed. We conclude that sexual behavior is controlled by loci other than those markers determining eye colors tested, and the genetic background for the mutant phenotypes is most critical for female discrimination.     

Age-dependent memory loss, synaptic pathology and altered brain plasticity in the Drosophila mutant cardinal accumulating 3-hydroxykynurenine

Summary. A search for Drosophila mutants with phenotypes similar to human diseases might help to unravel evolutionary conserved genes implicated in polygenic human disorders. Among these are neurodegenerative diseases, characterized by a late onset disturbance of memory, synaptic and glial pathology, structural brain impairments and altered content of the intermediates of the kynurenine pathway, the modulators of glutamate excito- and oxidative toxicity. This pathway is conserved in insects, in rodents, and in humans. We tested the Drosophila mutants cardinal (3-hydroxykynurenine excess) and cinnabar (kynurenic acid excess) for age-dependent changes in memory, synaptic pathology, structural brain plasticity and glial immunoreactivity. The mutant cardinal demonstrated a decline in learning and memory from the 12th to the 29th day of life in a paradigm of conditioned courtship suppression. Memory decline was accompanied by a sharp decrease in immunoreactivity to the synaptic cysteine string protein, and alterations in volumetric parameters of the mushroom bodies, the brain structures implicated in memory. Received February 22, 1999; accepted November 12, 1999     

Experience-mediated courtship reduction and competition for mates by maleDrosophila melanogaster

Previous research has described conditions which will alter the mating behavior of femaleDrosophila. MaleD. melanogaster exposed to mated females or immature males will show reduced levels of courtship toward normally attractive virgin females or immature males, respectively. Experiments allowing experienced and naive subject males to compete for virgin females are described. The results indicate that experience with mated females does not significantly alter the effectiveness of a male competing for a mate. However, experience with immature males can significantly increase the chances of securing a mate in some circumstances. These results are consistent with previous suggestions that learning phenotypes inD. melanogaster may be associated with evolutionary fitness.This work was supported by the National Science Foundation under Grants BSR-8411503 to S.Z. and DEB 81-18405 to R.C.R.     

The Drosophila Homologue of Tubulin-Specific Chaperone E–Like Protein Is Required for Synchronous Sperm Individualization and Normal Male Fertility

The tubulin-specific chaperone E–like protein (TBCEL or E-like) of vertebrates shows sequence homology to TBCE, a component of the multimolecular complex required for tubulin heterodimer formation in all eukaryotic cells. TBCEL apparently serves more specific functions, as it is found only in animals. At the cellular level, TBCEL plays a role as a regulator of tubulin stability. It is strongly expressed in human testes, but its systemic function is not known. The gene CG12214 codes for the Drosophila homologue of the vertebrate TBCEL protein. Here we show that disruption of the Drosophila Tbcel gene causes defects in spermatid individualixation, which leads to dispersed migration of F-actin–rich investment cones. Mutations affecting the Tbcel gene cause strong reduction in male, but not female, fertility. However, mature sperm function apparently is not impaired. We generated polyclonal antisera against TBCEL to study its localization and distribution in Drosophila tissues. Immunostainings of wild-type and null mutant testes demonstrated that TBCEL is localized in testes, presumably associated with axoneme bundles prior to spermatid individualization. Molecular analysis of the transposon insertion site in the mutant mulet (mlt), for which male sterility and sperm individualization defects have previously been described, demonstrates that the mlt P-element insertion resides in the Tbcel gene. Our results show that loss of TBCEL in Drosophila is compatible with viability and normal female fertility but causes reduced male fertility. We conclude that Drosophila TBCEL is strongly expressed in testes and plays an important role in sperm individualization during spermatogenesis. The high level of Tbcel mRNA in human testes suggests a general role of TBCEL in animal spermatogenesis. However, Western blots and courtship analysis suggest that TBCEL may have additional functions in the nervous system of Drosophila that could contribute to the observed reduced male fertility. These functions now have to be investigated.     

Effects of the Apterous Mutation on Drosophila Melanogaster Males' Courtship

The apterous⁴ (ap⁴) mutation has pleiotropic effects on the morphology and lifespan of D. melanogaster adults. The mutation also affects one aspect of male sexual behaviour. Unlike normal, sexually mature males, three day old ap⁴ lap⁴ males synthesize courtship-stimulating hydrocarbons that immature males make; as a result they elicit vigorous courtship (Jallon and Hotta, 1979; Jallon et al., 1986). Data presented in this report indicate that expression of the apterous⁴ mutation does not affect all aspects of sexual maturation in males. Specifically, 24-30 hour old ap⁴ jap⁴ males are capable of performing all of the courtship behaviors, including abdominal vibration, a newly described response of mutant and wild-type males to virgin females. However, the mutant males spend less time courting and are less likely to perform some of the courtship behaviours than age-matched controls. These abnormalities are probably indirect effects of the apterous⁴ allele's previously unreported effects on the flies' motor functions, which include partial paralysis, lack of coordination, and sluggishness.