Jacquelyn Cranney

Effects of D-cycloserine on extinction of conditioned freezing.

The present study tested the prediction that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, would facilitate extinction of conditioned freezing in male Sprague-Dawley rats. Rats received 5 light-shock pairings (conditioning). The following day, rats received 6 light-alone presentations (extinction training). Twenty-four hours later, rats received 1 light-alone presentation (test). Subcutaneous DCS injection before or after extinction training significantly enhanced extinction, and the dose-response curve for this effect was linear. Increasing the delay of DCS administration after extinction training led to a linear decrease in the facilitatory effect. The effect of systemic administration was replicated by intra-basolateral amygdala infusion. These results suggest that DCS facilitates extinction of conditioned freezing by acting on consolidation processes partly mediated by the basolateral amygdala.

d-cycloserine facilitates extinction of learned fear: Effects on reacquisition and generalized extinction

BACKGROUND d-cycloserine (DCS) facilitates extinction of learned fear. The aim of this study was to examine whether DCS 1) affects reacquisition of fear (Experiment 1) and 2) produces generalized extinction of fear (Experiment 2). METHODS Following fear conditioning, where a light or a tone conditioned stimulus (CS) was paired with a white-noise burst unconditioned stimulus (US), rats received nonreinforced exposure to one CS (i.e., extinction training). Fear was assessed by measuring CS-elicited freezing, a species-specific defense response. RESULTS Rats given DCS exhibited facilitated extinction of fear but were able to reacquire fear of that CS in a similar manner as saline-treated control animals (Experiment 1). Furthermore, DCS-treated rats exhibited generalized extinction (i.e., they were less fearful of a non-extinguished CS) in comparison to controls (Experiment 2). CONCLUSIONS DCS facilitates extinction of learned fear to the extinguished CS, but also appears to reduce fear of a nonextinguished CS. These findings suggest that this drug may have substantial clinical value in the treatment of anxiety disorders.

D-cycloserine and the facilitation of extinction of conditioned fear : Consequences for reinstatement

Several recent studies have reported that D-cycloserine (DCS), a partial N-methyl-D-aspartate agonist, facilitates extinction of learned fear in rats. Other studies have shown that representation of the unconditioned stimulus (US) can reinstate learned fear after extinction. This study examined whether this reinstatement effect occurs in Sprague-Dawley rats given DCS at the time of extinction. Results showed that saline-treated rats exhibited the reinstatement effect but DCS-treated rats did not (Experiments 1 and 2). This lack of reinstatement in DCS-treated rats was not due to residual effects of DCS on either US or context processing (Experiment 3). Overall, these results (a) raise questions about the mechanisms underlying DCS facilitation of extinction and (b) suggest that DCS might have substantial practical benefit.

Behavioral and Neural Analysis of GABA in the Acquisition, Consolidation, Reconsolidation, and Extinction of Fear Memory

The current review systematically documents the role of γ-amino-butyric acid (GABA) in different aspects of fear memory—acquisition and consolidation, reconsolidation, and extinction, and attempts to resolve apparent contradictions in the data in order to identify the function of GABAA receptors in fear memory. First, numerous studies have shown that pre- and post-training administration of drugs that facilitate GABAergic transmission disrupt the initial formation of fear memories, indicating a role for GABAA receptors, possibly within the amygdala and hippocampus, in the acquisition and consolidation of fear memories. Similarly, recent evidence indicates that these drugs are also detrimental to the restorage of fear memories after their reactivation. This suggests a role for GABAA receptors in the reconsolidation of fear memories, although the precise neural circuits are yet to be identified. Finally, research regarding the role of GABA in extinction has shown that GABAergic transmission is also disruptive to the formation of newly acquired extinction memories. We argue that contradictions to these patterns are the result of variations in (a) the location of drug infusion, (b) the dosage of the drug and/or (c) the time point of drug administration. The question of whether these GABA-induced memory deficits reflect deficits in retrieval is discussed. Overall, the evidence implies that the processes mediating memory stability consequent to initial fear learning, memory reactivation, and extinction training are dependent on a common mechanism of reduced GABAergic neurotransmission.

Influence of Long-Term Sensitization on Long-Term Habituation of the Acoustic Startle Response in Rats: Central Gray Lesions, Preexposure, and Extinction

The relation between long-term decrements of the acoustic startle response in rats and the development of freezing behavior during habituation training was examined. Freezing behavior developed over the initial trials of habituation training, and the rate of long-term response decrements was found to be inversely related to the development of freezing. Manipulations (neurological or behavioral) that either reduced the level of freezing or retarded its development promoted startle response decrements. In Experiment 1, rats receiving electrolytic lesions of the ventrolateral periaqueductal gray demonstrated both accelerated long-term startle response decrements and retarded development of freezing behavior. In Experiment 2, preexposure to the startle apparatus (i.e., latent inhibition) accelerated long-term startle decrements and inhibited development of freezing. In Experiment 3, exposure to the startle apparatus following initial habituation training (i.e., extinction) reduced both freezing behavior and startle response amplitudes. The results are discussed in terms of the influence of Pavlovian fear conditioning on long-term habituation of the acoustic startle response.

Potentiation of the Acoustic Startle Response by a Conditioned Stimulus Paired With Acoustic Startle Stimulus in Rats

The hypothesis that the standard acoustic startle habituation paradigm contains the elements of Pavlovian fear conditioning was tested. In a potentiated startle response paradigm, a startle stimulus and a light conditioned stimulus (CS) were paired. A startle stimulus then was tested alone or following the CS. Freezing behavior was measured to index conditioned fear. The startle response was potentiated on CS trials, and rats froze more in CS than in non-CS periods. In Experiment 1, response to a previously habituated, weak startle stimulus was potentiated. In Experiment 2, response to the same stimulus used as the unconditioned stimulus (US) in training was potentiated. This CS-potentiated response retarded the course of response decrements over training sessions as compared with an explictly unpaired control group. Conditioned fear is a standard feature of this habituation paradigm, serves to potentiate the startle response, and provides an associative dimension lacking in the habituation process per se.

Dopamine Antagonists in the Orbital Prefrontal Cortex Reduce Prepulse Inhibition of the Acoustic Startle Reflex in the Rat

Schizophrenia is characterized by, among other things, (a) information processing deficits that have been indexed by a number of measures, including deficits in prepulse inhibition (PPI) of the acoustic startle reflex; and (b) pathophysiology of the frontal lobe. Recent studies have implicated the prefrontal cortex (PFC) in the modulation of PPI in rats. These studies suggest that dopamine (DA) ablation of the PFC (using 6-OHDA) leads to disruption of PPI. To better understand the role of DA type 1 (D1) and type 2 (D2) receptors in the modulation of PPI, we investigated the effects of two pharmacologically distinct DA antagonists on the modulation of PPI. Microinjection of SCH23390 (a D1 antagonist) into the orbital PFC markedly decreased PPI (at 0.1, 0.5, and 1.5 microg), whereas raclopride (a D2 antagonist) decreased PPI at some doses (0.1 and 0.5 mg/ml) but not at others (5.0 microg). We conclude that both D1 and D2 receptors mediate the cortical modulation of PPI.

Breaking ground in cross-cultural research on the fear of being laughed at (gelotophobia): A multi-national study involving 73 countries

Abstract The current study examines whether the fear of being laughed at (gelotophobia) can be assessed reliably and validly by means of a self-report instrument in different countries of the world. All items of the GELOPH (Ruch and Titze, GELOPH〈46〉, University of Düsseldorf, 1998; Ruch and Proyer, Swiss Journal of Psychology 67:19–27, 2008b) were translated to the local language of the collaborator (42 languages in total). In total, 22,610 participants in 93 samples from 73 countries completed the GELOPH. Across all samples the reliability of the 15-item questionnaire was high (mean alpha of .85) and in all samples the scales appeared to be unidimensional. The endorsement rates for the items ranged from 1.31% through 80.00% to a single item. Variations in the mean scores of the items were more strongly related to the culture in a country and not to the language in which the data were collected. This was also supported by a multidimensional scaling analysis with standardized mean scores of the items from the GELOPH〈15〉. This analysis identified two dimensions that further helped explaining the data (i.e., insecure vs. intense avoidant-restrictive and low vs. high suspicious tendencies towards the laughter of others). Furthermore, multiple samples derived from one country tended to be (with a few exceptions) highly similar. The study shows that gelotophobia can be assessed reliably by means of a self-report instrument in cross-cultural research. This study enables further studies of the fear of being laughed at with regard to differences in the prevalence and putative causes of gelotophobia in comparisons to different cultures.

Effects of lesions of the cerebellar vermis on VMH lesion-induced hyperdefensiveness, spontaneous mouse killing, and freezing in rats ☆

In a series of independent experiments, we showed that lesions of the vermis of the cerebellum in rats blocked the hyperdefensiveness induced by lesions of the ventromedial hypothalamus (VMH), attenuated spontaneous mouse killing, and reduced unconditioned freezing and other signs of fear in the presence of a cat. The vermal lesions did not significantly affect foot-shock conditioned freezing. Control lesions of the cerebellar hemispheres did not affect VMH lesion-induced hyperdefensiveness or freezing in the presence of a cat. The hemispheric lesions did attenuate foot-shock conditioned freezing. The data are discussed in terms of the striking similarities and differences between the behavioral effects of cerebellar vermal lesions and amygdala lesions and the interaction of a number of brain areas in modulating agonistic behaviors. The results leave no doubt that the medial cerebellum is significantly involved in the control of species-specific agonistic behaviors. The specific dimension of agonistic behaviors and the details of the interactions with other brain areas remain a puzzle which we approached here by expanding the behavioral profile of animals with lesions of the cerebellar vermis.

The testing effect, collaborative learning, and retrieval-induced facilitation in a classroom setting

Two studies were conducted to investigate aspects of the test effect in a tertiary education setting. During weekly tutorial sessions first year psychology students watched a psychobiology video (Phase 1), followed by different video-related activities (Phase 2). In the tutorial 1 week later, students took an unexpected test (Phase 3). In Phase 2 of Study 1, students completed a quiz in small groups (group quiz) or individually (individual quiz), highlighted the video transcript (re-study), or did nothing further (no-activity). Group quiz performance was superior to individual quiz in both Phase 2 and Phase 3. In Phase 3 individual quiz students performed better than no-activity students, but not better than restudy students. In exploring the individual testing effect further, Phase 2 of Study 2 included quiz (individual), restudy, and no-activity conditions. Quiz participants were presented with one (target) of two sets of questions, whereas restudy participants were presented with equivalent statements. During Phase 3, all participants answered both sets of questions (target and related). Quiz performance was superior to restudy and no-activity performance on both target and related material, supporting the retrieval-induced facilitation explanation of the testing effect. Implications of the current research for assessment practices in classroom settings are discussed, and directions for future research are indicated.