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Background Rats reared in social isolation exhibit various cognitive and behavioural abnormalities in adulthood. However, impulsivity following this treatment still remains unclear, especially in response to medications used in attention deficit hyperactivity disorder, such as amphetamine. Methods Using an isolation-rearing (IR) manipulation, the present study examined the effects of IR on impulsive action and impulsive choice when also treated with doses of d-amphetamine, by employing the five-choice serial reaction time task (5-CSRTT) and a temporal discounting of reward task (TDRT), respectively. Results IR rats showed similar acquisition of the 5-CSRTT. Amphetamine increased premature responding in both groups; however, IR rats showed less responding overall. For the TDRT, IR rats revealed a greater preference for the large but delayed reward during task acquisition (i.e. were less impulsive) with a higher rate of nose poking during the delay, and exhibited a compressed dose-response function (i.e. reduced dose sensitivity) for amphetamine. Discussion Impulsive action and impulsive choice were reduced in IR rats under certain conditions, and a blunted response to d-amphetamine was found on these measures. These reductions in impulsivity contrast with locomotor hyperactivity normally shown in IR rats and the findings have implications for the utility of IR as a model of psychopathology. Electronic supplementary material The online version of this article (doi:10.1007/s00213-017-4579-8) contains supplementary material, which is available to authorized users.

Posttraumatic stress disorder (PTSD) is a trauma-induced mental disorder characterised by fear extinction dysfunction in which fear circuit monoamines are possibly associated. PTSD often coexists with depressive/anxiety symptoms, and selective serotonin reuptake inhibitors (SSRIs) are recommended to treat PTSD. However, therapeutic mechanisms of SSRIs underlying the PTSD fear symptoms remain unclear. Using a rodent PTSD model, we examined the effects of early SSRI intervention in mood and fear dysfunctions with associated changes of monoamines within the fear circuit areas. A 14-day escitalopram (ESC) regimen (5 mg/kg/day) was undertaken in two separate experiments in rats which previously received a protocol of single prolonged stress (SPS). In experiment 1, sucrose preference and elevated T-maze were used to index anhedonia depression and avoidance/escape anxiety profiles. In experiment 2, the percentage of freezing time was measured in a 3-day fear conditioning paradigm. At the end of our study, tissue levels of serotonin (5-HT) in the medial prefrontal cortex, amygdala, hippocampus, and striatum were measured in experiment 1, and the efflux levels of infralimbic (IL) monoamines were measured in experiment 2. In experiment 1, ESC corrected both behavioural (depression/anxiety) and neurochemical (reduced 5-HT tissue levels in amygdala/hippocampus) abnormalities. In experiment 2, ESC was unable to correct the SPS-impaired retrieval of fear extinction. In IL, ESC increased the efflux level of 5-HT but failed to reverse SPS-reduced dopamine (DA) and noradrenaline (NA). PTSD-induced mood dysfunction is psychopathologically different from PTSD-induced fear disruption in terms of disequilibrium of monoamines within the fear circuit areas.

Repeated injections of amphetamine (AMPH) can progressively augment behavioral responses, a phenomenon known as behavioral sensitization. AMPH-induced behavioral sensitization can be demonstrated in a rat model of schedule-induced polydipsia (SIP).The aim of this study was to investigate the effects of a nonspecific nitric oxide (NO) synthase inhibitor, N(G)-nitro arginine methyl ester (L: -NAME), on the AMPH sensitization effects in SIP.Rats were trained to establish SIP. The induction of AMPH sensitization in SIP was tested in either the home cage or a test cage. L: -NAME (50 mg/kg, i.p.) was co-administered with AMPH for five consecutive days, and its effect on induction was examined 3 and 14 days after withdrawal. The effect of L: -NAME on expression was examined on the final testing day by co-administration with AMPH in previously sensitized SIP rats.AMPH-induced behavioral sensitization in SIP rats only occurred when AMPH was injected in the home cage. Pretreatment with L: -NAME successfully blocked the induction of this sensitization following both short and long-term withdrawal. Once sensitization had been established, L: -NAME had no further influence.These results suggest that SIP behavior observed after repeated AMPH treatment is mediated by an NO-associated mechanism.

Individuals who experience sleep loss may exhibit certain physiological abnormalities. Central stimulant drugs have been studied in sleep-loss conditions, and some of them might be therapeutically beneficial. Modafinil (diphenyl-methyl-sulfinyl-2-acetamide, MOD) has been increasingly employed for elevating alertness and vigilance in recent years, yet the underlying mechanism of actions for MOD is not fully understood. To examine the behavioral effect of MOD following rapid eye movement sleep deprivation (REMD) in rats. A five-choice serial reaction time task (5-CSRTT) was employed to investigate animals’ attentional performance and impulsive reactivity. Rats of different ages were trained to learn the 5-CSRTT. REMD with the water platform method was applied for 96 h. The impacts of REMD on 5-CSRTT in middle-age (32-weeks-old) and young-adult (12-week-old) rats were compared with baseline or a condition with shorter visual stimulus duration. The results revealed that following REMD, young-adult but not middle-age rats were liable to be affected in their performances of the 5-CSRTT. In young-adult rats, while MOD had no contributions to the effect of REMD, it worsened rats’ performance following REMD when the stimulus duration was shortened, as shown by the reduced number of correct responses and prolonged magazine latency. These results suggest that aging might be a crucial factor for the physiological impact following REMD. MOD should be used cautiously, particularly, in conditions that require REM sleep.