The effects of chloropromazine and pentobarbital on behavior maintained by electric shock or point loss avoidance in humans

Human volunteer subjects were trained to press a lever to avoid or escape electric shock or loss of points which could be redeemed for money at the termination of the study. The effects of pentobarbital and chlorpromazine on avoidance and escape behavior were compared. Both aversive stimuli maintained behavior which was differentially sensitive to these two drugs. Chlorpromazine caused a decrease in avoidance responding at doses which had little effect on escape responding. Pentobarbital, in contrast, suppressed avoidance responding at doses which also had a suppressant effect on escape responding.This researched was supported by FDA No. 223-72-3042 (E. H. Uhlenhuth, Principal Investigator) and DA-00024 (C. R. Schuster, Principal Investigator).     

The influence of various neuroleptic drugs on noise escape response in rats

The effects of twenty neuroleptic drugs on noise escape behavior were studied in rats trained to interrupt an aversive noise (95 decibels recycling every 20 sec) by jumping, in a shuttle box, from one compartment into the other. All twenty drugs prolonged the latency (T) and reduced the frequency (F) of the noise escape response rate.Under the described experimental conditions, the order of potency of the 20 neuroleptics studied was: spiroperidol > spirilene trifluperidol > benperidol > droperidol > spiramide > clofluperol moperone > perphenazine > haloperidol fluphenazine > amiperone > trifluperazine > pimozide > thioperazine > triflupromazine fluanisone > chlorpromazine > pipamperone > thioridazine.For all compounds tested, T was more sensitive to drug effect than F.Using the F 45/T 900 ratio, the order of specificity of the compounds studied was: pimozide > benperidol spirilene clofluperol > trifluperidol haloperidol fluphenazine spiroperidol = perphenazine moperone = trifluperazine = thioperazine spiramide > amiperone droperidol > triflupromazine chlorpromazine fluanisone > thioridazine pipamperone.As far as potency was concerned, there was a good correlation (r=0.974) between the F 900-values of the noise escape test and the ED₅₀-values in the nondiscriminated Sidman avoidance test in rats and, as far as sedative properties were concerned, between the F 45/T 900 ratio and the palpebral ptosis/catalepsy ratio (r = –0.960) of the observation test in rats.     

Stimulus-response relationships in a quickly learned escape from shock: effects of morphine

The relationship between stimulus intensity and analgesic effectiveness of morphine was investigated by means of an operant technique. Various doses of morphine were tested in rats trained to press a bar to escape from shocks of varying intensity. Under control conditions a good linear relationship between the log of the stimulus intensity and the log of the speed to press the lever was found. Morphine showed inhibitory effects upon this escape behavior, which were greater at any given dose with greater intensity of the shock. These effects were dose related, that is, the slopes of the shock-response lines decreased by increasing the dose. The data obtained do not appear to be a consequence of a general depressant effect of the drug upon behavior and are in line with several experimental observations showing that in animals, as well as in humans, the magnitude of the analgesic effect of morphine tends to increase as pain severity increases.     

An examination of the effects of stimulant and depressant drugs on escape/avoidance conditioning in strains of rats selectively bred for emotionality/non-emotionality

Summary Two of the main hypotheses concerning the role of emotionality (as an excitatory state) in the determination of escape/avoidance conditioning are juxtaposed, and their explanatory force tested by the use of constitutionally differentiated levels of reactivity in rats and the interaction these constitutional states may have with different drugs (assumed to affect different neural structures) and different doses of such drugs. From an analysis of these main effects and their interactions a complex set of relationships emerge which suggest that all the variables employed, with the exception of sex, are likely to be relevant to a consideration of those factors subserving differences in conditioning and learning.This experiment is part of the thesis submitted to the University of London in 1967 in partial fulfilment of the degree of Ph.D. in Psychology under the guidance of Professor H. J. Eysenck and Dr. H. C. Holland.     

Interactions between aversive and rewarding effects of hypothalamic stimulations

Interactions between aversive and rewarding effects of brain stimulations were studied by assessing the variation of both escape and approach responses induced in a shuttle box by applying electrical stimulations of various intensities simultaneously to a medial hypothalamic (MH) site and to a lateral hypothalamic (LH) site. The results obtained show that: (1) LH stimulation produces two effects whose relative strengths appear to depend on both the location of the stimulation site and the intensity applied: (a) a suppressant effect correlated with the rewarding effect, which reduces MH escape responding; and (b) an enhancing effect correlated with the aversive effect, which increases MH escape responding. (2) MH stimulation similarly produces two effects whose relative strengths vary with both the location of the stimulation site and the intensity applied: (a) an enhancing effect which increases LH approach responding and (b) a suppressant effect which decreases LH approach responding. (3) The above-mentioned effects occur irrespective of whether the two stimulation sites (MH and LH) are ipsi- or contralateral to each other. These results suggest that the effects of LH stimulation on MH induced escape as well as those of MH stimulation on LH induced approach are related to the affective (aversive, rewarding) properties of the stimulation.     

Decours temporel des effets aversif et appetitif induits par stimulation intracerebrale

When given the possiblity to do so, a rat switches on (approach response) and then switches off (escape response) an electrical stimulation applied to the medial (HM) or to the lateral (HL) hypothalamus. In the case of a discontinuous stimulation consisting of a succession of stimulation trains, variations affecting train duration (DT) or intertrain interval (IIT) are found to affect differentially the escape latency (appraised by the stimulation time ts) and the approach latency (appraised by the nonstimulation time tns). (a) If it is the escape latency (ts) that is to be maintained at a constant level of performance, any increase of IIT must be compensated for by an increase of DT. The relation between IIT and DT thus established appears to be of the same type, irrespective of whether the stimulation is being applied to a HM or HL site, or else to sites located in the dorsal part of the mesencephalic central gray (GC) where the rat switches off the stimulation without spontaneously restarting it. This observation suggests that similar processes are brought into play whenever a stimulation applied to one of the structures studied (HM, HL, GC) induces the rat to switch it off. (b) If it is the approach latency (tns) that is to be maintained at a constant level of performance, an increase of IIT has no longer to be compensated for by an increase of DT, as soon as DT gets longer than 0.3–0.5 sec. This observation suggests that the two effects that both result from one and the same brain stimulation and that express themselves in an escape response and in an approach response, respectively, differ from one another with regard to their time course.     

Anxiety-like behaviors produced by acute fluoxetine administration in male Fischer 344 rats are prevented by prior exercise

RATIONALE: Although selective 5-HT reuptake inhibitors (SSRIs) can reduce anxiety after chronic treatment, acute SSRI administration is associated with an increase in anxiety consistent with an acute increase in 5-HT neurotransmission. Exercise is anxiolytic in humans, and wheel running prevents anxiety-like behavioral consequences of uncontrollable stress in rats, but the effects of exercise on acute fluoxetine-induced anxiety-like behaviors are unknown. OBJECTIVES: The current studies tested the hypothesis that acute administration of the SSRI fluoxetine would produce behaviors in rats resembling those produced by uncontrollable stress and that these behaviors would be blocked by prior wheel running. RESULTS: Adult, male Fisher 344 rats administered moderate (10 mg/kg) or high (20 mg/kg) doses of fluoxetine demonstrated exaggerated shock-elicited freezing and an interference with shuttle box escape compared to rats given either saline or low-dose fluoxetine (2.5 mg/kg). Fluoxetine-induced behaviors were similar to, but smaller in magnitude than, those produced by uncontrollable stress and were blocked by pretreatment with the 5-HT(2C) receptor antagonist SB 242084 (1 mg/kg). Rats allowed access to running wheels for 6 weeks were protected against the anxiety-like behaviors produced by a single injection of fluoxetine (10 mg/kg). CONCLUSIONS: Behavioral effects of acute fluoxetine administration resemble those produced by uncontrollable stress. Results are consistent with the idea that exercise can produce resistance against the anxiogenic effects of acute increases in 5-HT and suggest that acute behavioral effects of antidepressants can depend on history of physical activity.     

Effects of sequence changes in the HIV-1 gp41 fusion peptide on CCR5 inhibitor resistance

A rare pathway of HIV-1 resistance to small molecule CCR5 inhibitors such as Vicriviroc (VCV) involves changes solely in the gp41 fusion peptide (FP). Here, we show that the G516V change is critical to VCV resistance in PBMC and TZM-bl cells, although it must be accompanied by either M518V or F519I to have a substantial impact. Modeling VCV inhibition data from the two cell types indicated that G516V allows both double mutants to use VCV-CCR5 complexes for entry. The model further identified F519I as an independent determinant of preference for the unoccupied, high-VCV affinity form of CCR5. From inhibitor-free reversion cultures, we also identified a substitution in the inner domain of gp120, T244A, which appears to counter the resistance phenotype created by the FP substitutions. Examining the interplay of these changes will enhance our understanding of Env complex interactions that influence both HIV-1 entry and resistance to CCR5 inhibitors.     

Stable seroepidemiology of hepatitis B after universal immunization in Taiwan: A 3-year study of national surveillance of primary school students

Background

This study is aimed to investigate if there was increased risk of HBV acquisition among first graders in Taiwan during a 3-year follow-up period.

Methods

A total of 1545 healthy first graders, who were vaccinated against HBV in infancy, were recruited in 2005. All subjects were checked for hepatitis B surface antigens (HBsAg), antibodies to HBsAg (anti-HBs), and to the hepatitis B core antigen (anti-HBc). Nucleotide sequence of the “a” determinant of HBsAg was determined by polymerase chain reaction and direct sequencing in the HBsAg carriers.

Results

Among 1545 subjects, 0.78% were HBsAg seropositive, 54.30% were anti-HBs seropositive, and 1.68% anti-HBc seropositive. Three of the 10 HBV carriers (30%), whose HBV DNA were sequenced for the S gene, had surface antigen mutants at the “a” determinant.

Conclusion

There were no new chronic HBV infections in this cohort of children for two consecutive years. HBV S gene vaccine escape mutants did exist in the vaccine-failure population, but they may not have made a major health impact.     

Children's hedonic responses to the odors of alcoholic beverages: a window to emotions.

The present study of 145 children and their mothers aimed to determine whether children's responses to the odors of alcoholic beverages were related to their mothers' reasons for drinking. Mothers completed a series of questionnaires to describe the emotional context in which they drink and whether they use alcohol to "escape" by changing their state of mind and reducing feelings of dysphoria. Children participated in two age-appropriate tasks that focused on the most salient psychological attribute of an odor, its perceived hedonic valence. To this aim, we determined children's liking, reaction times, and identification of individual odors including beer and whiskey in Task 1, and their preference for beer relative to odors that differed in hedonic valence in Task 2. The type of task and behavioral measure revealed different aspects of children's responses, to alcohol odors. In Task 1, verbally identifying an odor was a more difficult task than deciding whether they liked the odor. Although there were few group differences in liking for individual odors, children of Escape drinkers took significantly longer to determine whether they liked the odors. In Task 2, children of Escape drinkers preferred beer less often, particularly when it was compared with less pleasant odors. They preferred coffee to beer odors and, if their mothers did not smoke cigarettes, preferred the odors of cigarette smoke and pyridine to beer. These children experienced the odor of alcohol more frequently and in the context of mood disturbed mothers who felt guilty and worried about their drinking. Whether children who associate the odor of alcohol with such emotional contexts display a trajectory toward or against using alcohol to escape remains unknown.