The relationship between cerebral asymmetry and measures of psychopathy in a non-clinical sample is moderated by both empathic challenge and biological sex.

This study investigated the relationship between psychopathy, as assessed by the Levenson Self-Report Psychopathy (LSRP) scale, and cerebral laterality. EEG recordings from frontal cortex (L3 and L4) were taken during both resting conditions and while viewing a video of an emergency field amputation, used as an empathic challenge. The ratio of alpha power from the two recording site was taken as an index of relative activity in the two hemispheres. Eighty three students from the University subject pool were recruited as participants. Male participants had a significantly higher mean LSRP score than did female participants. While LSRP scores were unrelated to cerebral laterality under resting conditions, there was both a significant linear and quadratic negative relationship between LSRP scores and relative left-hemisphere alpha activity. As alpha activity has been reported to be inversely related to brain or mental activity, a negative relationship can be inferred between LSRP scores and right hemisphere neural activity. The female participants had a much stronger quadratic relationship than did the combined sample, while the male sample showed only weak, non-significant relationships. Our data suggest that the relationship between psychopathy and cerebral laterality may be sexually dimorphic.

Ketamine modulates TRH and TRH-like peptide turnover in brain and peripheral tissues of male rats.

Major depression is the largest single healthcare burden with treatments of slow onset and often limited efficacy. Ketamine, a NMDA antagonist used extensively as a pediatric and veterinary anesthetic, has recently been shown to be a rapid acting antidepressant, making it a potential lifesaver for suicidal patients. Side effects and risk of abuse limit the chronic use of ketamine. More complete understanding of the neurobiochemical mechanisms of ketamine should lead to safer alternatives. Some of the physiological and pharmacological actions of ketamine are consistent with increased synthesis and release of TRH (pGlu-His-Pro-NH2), and TRH-like peptides (pGlu-X-Pro-NH2) where "X" can be any amino acid residue. Moreover, TRH-like peptides are themselves potential therapeutic agents for the treatment of major depression, anxiety, bipolar disorder, epilepsy, Alzheimer's and Parkinson's diseases. For these reasons, male Sprague-Dawley rats were anesthetized with 162 mg/kg ip ketamine and then infused intranasally with 20 µl of sterile saline containing either 0 or 5 mg/ml Glu-TRH. One, 2 or 4h later, the brain levels of TRH and TRH-like peptides were measured in various brain regions and peripheral tissues. At 1h in brain following ketamine only, the levels of TRH and TRH-like peptides were significantly increased in 52 instances (due to increased biosynthesis and/or decreased release) or decreased in five instances. These changes, listed by brain region in order of decreasing number of significant increases (↑) and/or decreases (↓), were: hypothalamus (9↑); piriform cortex (8↑); entorhinal cortex (7↑); nucleus accumbens (7↑); posterior cingulate (5↑); striatum (4↑); frontal cortex (2↑,3↓); amygdala (3↑); medulla oblongata (1↑,2↓); cerebellum (2↑); hippocampus (2↑); anterior cingulate (2↑). The corresponding changes in peripheral tissues were: adrenals (8↑); epididymis (4↑); testis (1↑,3↓); pancreas (1↑); prostate (1↑). We conclude that TRH and TRH-like peptides may be downstream mediators of the rapid antidepressant actions of ketamine.

The Behavioral Physiology and Antidepressant Mechanisms of Electroconvulsive Shock.

OBJECTIVE: This study aimed to determine whether the association between antidepressant (AD) and anticonvulsant effects of electroconvulsive therapy constitutes a necessary, causal relationship. METHODS: The rats received corneal kindling to induce an epileptic focus, whereas electroconvulsive shock (ECS) was given antagonistically. The forced swim test (FST; a model of AD efficacy), cumulative kindling scores (indexing epileptogenesis), and clonus duration (measuring anticonvulsant effects) were used to assess the effects of ECS. Intensity and route of administration (corneal vs pinnate) of ECS were varied within or across 2 experiments. RESULTS: Under various conditions, an increase in mobility in the FST (an index of AD properties) was observed in the absence of any retardation of kindling; under other conditions, an antiepileptogenic effect occurred in the absence of any change in immobility in the FST. In addition, 2 forms of ECS treatment had equal AD properties, whereas only 1 of the 2 treatments reduced clonus time (suggesting an elevated seizure threshold). CONCLUSIONS: In a rat model, putative AD effects of ECS are dissociable from its antiepileptogenic and anticonvulsant effects, suggesting different stimulus thresholds for the various effects of corneal ECS: the antiepileptogenic effect required a lower current dose than the behavioral effect in the FST, whereas the anticonvulsant effect required the highest stimulation level. With transpinnate ECS, the threshold for the behavioral effect in the FST and the antiepileptogenic threshold were reversed.

TRH-like antidepressant peptide, pyroglutamyltyroslyprolineamide, occurs in rat brain.

We have previously reported the occurrence of pGlu-Glu-Pro-NH(2)(Glu-TRH, EEP), Val-TRH, Tyr-TRH, Leu-TRH, Phe-TRH, and Trp-TRH in rat brain using a combination of HPLC and radioimmunoassays with antibodies that cross-react with the general structure pGlu-X-Pro-NH(2) where 'X' maybe any amino acid residue (Peptides 2004; 25 : 647). This new family of TRH-like peptides, along with TRH (pGlu-His-Pro-NH(2)), has neuroprotective, anticonvulsant, antidepressant, euphoric, anti-amnesic, and analeptic effects. We now report that a combination of affinity chromatography using a rabbit antibody specific for Tyr-TRH and Phe-TRH, along with HPLC and tandem mass spectrometry operating in the multiple reaction monitoring (MRM) mode, provide conclusive evidence for the presence of Tyr-TRH in rat brain. Furthermore, synthetic Tyr-TRH is active in the Porsolt Swim Test suggesting that it is a fourth member of this family of in vivo neuroregulatory agents that have psychopharmacotherapeutic properties.