GABA(A) receptor neurotransmission dysfunction in a mouse model of social isolation-induced stress: possible insights into a non-serotonergic mechanism of action of SSRIs in mood and anxiety disorders

Protracted social isolation in laboratory animals causes stress, which induces a variety of behavioral abnormalities including increased aggressiveness, anxiety-related behaviors, cognitive deficits and hyper locomotion. Many of these disorders are similar to the symptoms found in psychiatric disorders, such as depression, anxiety, premenstrual dysphoria and posttraumatic stress disorders (PTSD). Recent studies have demonstrated that male mice that have been socially isolated for more than 4 weeks show: (a) reduced responsiveness of GABA(A) receptors (GABA(A)-R) to the administrations of GABA mimetic drugs at GABA(A)-R; (b) downregulated biosynthesis of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP) (allopregnanolone: ALLO), a neurosteroid with a potent positive allosteric modulatory effect on the action of GABA on GABA(A)-R; and (c) alterations in the expression of GABA(A)-R subunits (i.e. a decrease of alpha1/alpha2 and gamma2 subunits and an increase of alpha4 and alpha5 subunits). The selective serotonin reuptake inhibitor (SSRI) fluoxetine (FLX) and its congener norfluoxetine (Nor-FLX), when administered systemically at nmol/kg doses, normalize the reduced content of brain ALLO and the reduced responsiveness of GABA(A)-R to GABA mimetic drugs (i.e. pentobarbital) and also attenuate aggressive behavior in socially isolated mice in a stereospecific manner. Although these compounds inhibit ex vivo serotonin reuptake into brain tissue, their SSRI activities require high micromol/kg dose ranges and are not stereospecific. These studies suggest that in socially isolated mice, abnormalities of GABA(A)-R signal transduction are attributable to the downregulation of ALLO production and to a switch in heteropentameric GABA(A)-R subunit assembly composition. Hence, the normalization of ALLO biosynthesis may be a new target for the development of drugs effective for psychiatric disorders related to neurosteroid biosynthesis downregulation.     

What is an affective artifact? A further development in situated affectivity

In this paper I would like to propose the notion of “affective artifact”, building on an analogy with theories of cognitive artifacts (cf. Casa     

Neural correlates of attention to emotional facial expressions in dysphoria

The present study investigated whether dysphoric individuals have a difficulty in disengaging attention from negative stimuli and/or reduced attention to positive information. Sad, neutral and happy facial stimuli were presented in an attention-shifting task to 18 dysphoric and 18 control participants. Reaction times to neutral shapes (squares and diamonds) and the event-related potentials to emotional faces were recorded. Dysphoric individuals did not show impaired attentional disengagement from sad faces or facilitated disengagement from happy faces. Right occipital lateralisation of P100 was absent in dysphoric individuals, possibly indicating reduced attention-related sensory facilitation for faces. Frontal P200 was largest for sad faces among dysphoric individuals, whereas controls showed larger amplitude to both sad and happy as compared with neutral expressions, suggesting that dysphoric individuals deployed early attention to sad, but not happy, expressions. Importantly, the results were obtained controlling for the participants' trait anxiety. We conclude that at least under some circumstances the presence of depressive symptoms can modulate early, automatic stages of emotional processing.     

Role of the dorsal hippocampus in object memory load

The dorsal hippocampus is crucial for mammalian spatial memory, but its exact role in item memory is still hotly debated. Recent evidence in humans suggested that the hippocampus might be selectively involved in item short-term memory to deal with an increasing memory load. In this study, we sought to test this hypothesis. To this aim we developed a novel behavioral procedure to study object memory load in mice by progressively increasing the stimulus set size in the spontaneous object recognition task. Using this procedure, we demonstrated that naive mice have a memory span, which is the number of elements they can remember for a short-time interval, of about six objects. Then, we showed that excitotoxic selective lesions of the dorsal hippocampus did not impair novel object discrimination in the condition of low memory load. In contrast, the same lesion impaired novel object discrimination in the high memory load condition, and reduced the object memory span to four objects. These results have important heuristic and clinical implications because they open new perspective toward the understanding of the role of the hippocampus in item memory and in memory span deficits occurring in human pathologies, such as Alzheimer's disease and schizophrenia.     

Eye gaze cannot be ignored (but neither can arrows)

Recent studies have tried to shed light on the automaticity of attentional shifts triggered by gaze and arrows with mixed results. In the present research, we aimed at testing a strong definition of resistance to suppression for orienting of attention elicited by these two cues. In five experiments, participants were informed with 100% certainty about the future location of a target they had to react to by presentation of either a direction word at the beginning of each trial or instructions at the beginning of each block. Gaze and arrows were presented before the target as uninformative distractors irrelevant for the task. The results showed similar patterns for gaze and arrows-namely, an interference effect when the distractors were incongruent with the upcoming target location. This suggests that the orienting of attention mediated by gaze and arrows can be considered as strongly automatic.     

Attention control and susceptibility to hypnosis

The present work aimed at assessing whether the interference exerted by task-irrelevant spatial information is comparable in high- and low-susceptible individuals and whether it may be eliminated by means of a specific posthypnotic suggestion. To this purpose high- and low-susceptible participants were tested using a Simon-like interference task after the administration of a suggestion aimed at preventing the processing of the irrelevant spatial information conveyed by the stimuli. The suggestion could be administered either in the absence or following a standard hypnotic induction. We showed that, outside from the hypnotic context, the Simon effect was similar in high and low-susceptible participants and it was significantly reduced following the posthypnotic suggestion in high-susceptible participants only. These results show that a specific posthypnotic suggestion can alter information processing in high-susceptible individuals and reduce the interfering effect exerted by arrow stimuli.