Andrew Chih Wei Huang

Anxiety- and depressive-like responses and c-fos activity in preproenkephalin knockout mice: oversensitivity hypothesis of enkephalin deficit-induced posttraumatic stress disorder.

The present study used the preproenkephalin knockout (ppENK) mice to test whether the endogenous enkephalins deficit could facilitate the anxiety- and depressive-like symptoms of posttraumatic stress disorder (PTSD). On Day 1, sixteen wildtype (WT) and sixteen ppENK male mice were given a 3 mA or no footshock treatment for 10 seconds in the footshock apparatus, respectively. On Days 2, 7, and 13, all mice were given situational reminders for 1 min per trial, and the freezing response was assessed. On Day 14, all mice were tested in the open field test, elevated plus maze, light/dark avoidance test, and forced swim test. Two hours after the last test, brain tissues were stained to examine c-fos expression in specific brain areas. The present results showed that the conditioned freezing response was significant for different genotypes (ppENK vs WT). The conditioned freezing effect of the ppENK mice was stronger than those of the WT mice. On Day 14, the ppENK mice showed more anxiety- and depressive-like responses than WT mice. The magnitude of Fos immunolabeling was also significantly greater in the primary motor cortex, bed nucleus of the stria terminalis-lateral division, bed nucleus of the stria terminalis-supracapsular division, paraventricular hypothalamic nucleus-lateral magnocellular part, central nucleus of the amygdala, and basolateral nucleus of the amygdala in ppENK mice compared with WT mice. In summary, animals with an endogenous deficit in enkephalins might be more sensitive to PTSD-like aversive stimuli and elicit stronger anxiety and depressive PTSD symptoms, suggesting an oversensitivity hypothesis of enkephalin deficit-induced PTSD.

Effects of stress, depression, and their interaction on heart rate, skin conductance, finger temperature, and respiratory rate: sympathetic‐parasympathetic hypothesis of stress and depression

We examined effects of stress, depression, and their interaction on sympathetic-parasympathetic responses, including percentage heart rate (PHR), percentage skin conductance (PSC), percentage finger temperature (PTEMP), and percentage respiratory rate (PRESPR). Participants were categorized into normal, low-risk, and high-risk depression groups under stress or no-stress by measuring psychophysiological responses. Stress increased PHR and PSC and decreased PTEMP. Depression negatively correlated with PHR and PTEMP. PSC and PTEMP were significantly dependent on and positively correlated with depression. PTEMP was significantly affected by the stress and depression interaction. Stress affects sympathetic, rather than parasympathetic, activity. Depression and the interaction between stress and depression initially associated with the sympathetic division and are then correlated with parasympathetic activity. A sympathetic-parasympathetic hypothesis and its clinical implications are discussed.

Neural substrates of fear conditioning, extinction, and spontaneous recovery in passive avoidance learning: a c-fos study in rats.

Extinguishing fear conditioning and preventing the return of fear are the goal in the treatment of anxiety disorders. However, the neural substrates that mediate fear conditioning, extinction, and spontaneous recovery (i.e., the return of fear) remain uncertain. We utilized the aversive passive avoidance learning paradigm and Fos-like immunoreactivity to elucidate this issue. Exception for naïve rats that did not receive any treatment served as the control group, the other rats were subjected to three sessions of context/footshock (0.5 mA, 2s) pairings followed by 12 extinction sessions (context-no footshock). After the last extinction test, these rats were assigned to one of three groups reflecting the number of resting days before the test session (context-no footshock): Day 8, Day 9, and Day 10 groups. Only the Day 10 group exhibited spontaneous recovery during the test session. Fos-like immunoreactivity associated with fear conditioning was seen in the amygdala and cingulate cortex area 1 (Cg1). The extinction of fear was seen to be related to Cg1, cingulate cortex area 2 (Cg2), piriform cortex (Pir), and entorhinal cortex (Ect). Spontaneous recovery was seen to be related to amygdala, Pir, and Ect. The present findings indicate that the brain substrates of fear acquisition, extinction and spontaneous recovery have different ensembles of brain activations. These differences suggest that different brain targets may be considered for fear extinction and for avoiding the return of fear in anxiety disorders.

Paradoxical simultaneous occurrence of amphetamine-induced conditioned taste aversion and conditioned place preference with the same single drug injection: A new “pre- and post-association” experimental paradigm

The paradoxical phenomenon of co-existing physically aversive and psychologically rewarding effects of drugs is a crucial issue for drug addiction. The present study employed a new experimental paradigm to test whether the rewarding and aversive properties of amphetamine (AMPH) can exist simultaneously. Rats were given a 15 min period of exposure to saccharin injected with 0.15M NaCl or 1.5mg/kg AMPH and then were confined to one compartment of a test box for 30 min. After three paired and unpaired cycles, the aversive and rewarding effects were assessed. A reduction in consumption of the paired flavored solution provided evidence of avoidance while preference for the AMPH injection context provided evidence of rewarding effects. The present findings demonstrate that the development of AMPH-induced rewarding and aversive effects depends on the particular behavioral conditions and support both the task-dependent drug effects hypothesis and the reward comparison hypothesis. The formation of associations with stimuli that comes before (pre) vs. after (post) the unconditioned stimulus and the role of the dopaminergic system in such associations are discussed.

Effects of single and group housing conditions and alterations in social and physical contexts on amphetamine-induced behavioral sensitization in rats

Repeated administration of amphetamine (AMPH) can produce behavioral sensitization. However, whether contextual elements and housing conditions influence AMPH-induced behavioral sensitization remains uncertain. This study was designed to examine the effects of housing conditions (single- vs. group-housed) and different contextual changes, including social (with two other co-drug partners) and physical (novel box) context changes, on AMPH-induced behavioral sensitization. During the training phase, all rats were exposed for 7 days to AMPH (1mg/kg, intraperitoneally) in a Locometer chamber, with the exception of animals tested for the effects of physical context changes trained in a novel box. Following a 7-day withdrawal phase, all rats received an AMPH (0.5mg/kg) challenge, and locomotor activity in a Locometer box was recorded before and after AMPH injection during the testing phase. Under group housing conditions, animals exposed to a different physical environment between the training and testing phases or accompanying co-drug partners during the training phase exhibited decreased AMPH-induced locomotor sensitization. In contrast, single housing conditions did not have an inhibitory effect on AMPH-induced behavioral sensitization after manipulations of the physical and social contexts. These results suggest that under group housing conditions, both physical and social context changes can attenuate AMPH-induced behavioral sensitization. The possible neural mechanisms underlying the involvement of different housing conditions in AMPH-induced behavioral sensitization are discussed.

Dose-dependent dissociable effects of haloperidol on locomotion, appetitive responses, and consummatory behavior in water-deprived rats

UNLABELLED We studied whether a cascade of different phases of ingestive behavior were governed by different doses of the dopamine D2 receptor system. A wide spectrum of doses (0, 0.025, 0.05, 0.1, 0.2, and 0.4mg/kg) of a D2 receptor antagonist, haloperidol, were administered to 6 groups of water-deprived rats. 45min following administration of the drug a 15min water intake session was allowed to assess the effect on (a) locomotion, (b) appetitive response and (c) consummatory responses. The procedure was repeated for 5days. RESULTS The doses of 0.025 to 0.1mg/kg had no effects on any measured behavior compared with the control group. The 0.2mg/kg dose induced catalepsy during sessions 3 and 5 and impaired consummatory (decreased lick numbers and intake volume) behaviors during sessions 1-5. The 0.4mg/kg dose affected appetitive behavior (increased latency to contact the water tube) during session 2 and consummatory behavior during all five water sessions. The 0.2mg/kg dose appeared to dissociate appetitive and consummatory behavior, and the 0.4mg/kg dose locomotor activity and motivational behavior (including consummatory and appetitive responses). These results, that the three elements of ingestive behavior (locomotion, appetitive responses, and consummatory behavior) have different sensitivity to haloperidol, suggest that separable D2 mechanisms are involved in governing the ingestive behavior.

Effects of lithium and carbamazepine on spatial learning and depressive behavior in a rat model of bipolar disorder induced by ouabain

Lithium (LiCl) and carbamazepine (CBZ), the common mood stabilizers, are thought to be effective treatments for bipolar disorder. The aim of the present study was to investigate whether LiCl as well as CBZ has similar effects on the bipolar disorder-associated cognitive dysfunctions in rats, particularly the spatial learning and depressive responses. Adult male Wistar rats were administered intracerebroventricularly with 5μl of 10(-3)M ouabain on session 1, and then received an intraperitoneal injection of LiCl or CBZ for 4 sessions (1 session/2days). For the behavioral tests, all rats were subjected to the water maze 15min for spatial learning and the forced swimming test 5min for depression on each session. The present results showed that ouabain resulted in increased latency and longer distance traveled to reach the hidden platform in the water maze, indicating that ouabain impaired the spatial learning. However, ouabain did not affect swimming velocity in the water maze and depressive responses in the forced swimming test. LiCl treatment decreased the ouabain-enhanced latency and the total distance, but not the velocity, swam to reach the hidden platform in the water maze task. Additionally, LiCl did not result in changes of any depressive indices, such as struggling behavior, swimming behavior, and floating behavior. Likewise, CBZ did not affect any behavioral indices of spatial learning and depression. A linear regression analysis suggested that LiCl, but not CBZ, could predict the decreased latency and total distance traveled except the velocity of swimming in the water maze and depressive behaviors. In summary, the present results suggested that lithium provided a better therapeutic effect than CBZ for ouabain-caused dysfunctions of spatial learning in a rat model of bipolar disorder.

Internet abusers associate with a depressive state but not a depressive trait

The present study investigated three issues: (i) whether Internet abusers display a depressive state without a depressive trait; (ii) which symptoms are shared between Internet abuse and depression; and (iii) which personality characteristics were shown in Internet abusers.

Roles of corticosterone in formalin-induced conditioned place aversion in rats.

Glucocorticoid hormones have been shown to contribute to many cognitive functions, such as depressions, learning and memory, and abnormal glucocorticoid secretion results in functional changes in prefrontal cortex and amygdala. In the present study, we used the conditioned place aversion (CPA) paradigm to investigate the role of corticosterone (CORT) in the negative affective component of chemical somatic pain induced by intraplantar injection of formalin into male adult Long-Evan rats. Five percent of formalin produced acute biphasic nociceptive behaviors, including flinching and licking of hindpaw, and CPA. Intraplantar formalin induced CPA was abolished by bilateral adrenalectomy and the impairment of CPA can be restored by the CORT treatment. However, the adrenalectomy failed to affect the formalin-produced acute nociceptive behaviors. Therefore, data from the present study suggest that CORT secretion by the adrenal cortex may play a role in chemical somatic noxious stimuli-induced avoidance learning and aversive memory, but not sensory discrimination of noxious stimulation.

Effects of thalamic hemorrhagic lesions on explicit and implicit learning during the acquisition and retrieval phases in an animal model of central post-stroke pain

HighlightsVBC lesions induced thermal hyperalgesia for acquisition and retrieval phases.VBC lesions facilitated conditioned place preference in implicit memory.VBC lesions did not affect spatial learning in explicit memory.VBC lesions did not affect motor function.Our data provide some insights for CPSP and learning memory. ABSTRACT Hemorrhagic stroke has many symptoms, including central pain, learning and memory impairments, motor deficits, language problems, emotional disturbances, and social maladjustment. Lesions of the ventral basal complex (VBC) of the thalamus elicit thermal and mechanical hyperalgesia, forming an animal model of central post‐stroke pain (CPSP). However, no research has yet examined the involvement of learning and memory in CPSP using an animal model. The present study examined whether VBC lesions affect motor function, conditioned place preference (CPP; implicit memory), and spatial learning (explicit memory) in the acquisition and retrieval phases. The results showed that rats with VBC lesions exhibited thermal hyperalgesia in the acquisition and retrieval phases, indicating that these lesions can induce CPSP. During these phases, the rats with VBC lesions exhibited enhanced (morphine‐induced) CPP learning. These lesions did not affect the rats’ total distance travelled, time spent, or velocity in the spatial learning tasks. The lesions also did not affect motor function in the rotarod task. Altogether, VBC lesions resulted in CPSP and facilitated CPP (implicit memory). However, the lesions did not affect spatial learning (explicit memory) or motor function. The relationship between CPSP and learning and memory is important for patients who suffer from such central pain. The implications of the present study may provide insights into helping reduce CPSP and its associated symptoms.