Null Mutation of the Arginine-Vasopressin Gene in Rats Slows Attentional Engagement and Facilitates Response Accuracy in a Lateralized Reaction Time Task

Abstract

The neurophysin vasopressin is thought to play an important role in emotional behavior and aspects of cognition in the rat, and the pathophysiology of this system has been implicated in two neurodevelopmental disorders, namely autism and schizophrenia. Genetic deficiency of vasopressin in rats, resulting from a null mutation of the vasopressin gene, causes alterations of brain development with resulting behavioral and neurochemical phenotypes in adulthood. We previously demonstrated that partial vasopressin deficiency (rats heterozygous for the null mutation) produces enhanced visuospatial attention and motor speeding. Here, the results of studies of homozygous Brattleboro rats that are fully vasopressin deficient are reported. We trained subjects to perform a lateralized reaction time task that measures visuospatial divided attention; in task conditions in which the duration of target stimuli was varied from trial to trial, homozygous Brattleboro rats showed a performance phenotype that consisted of more accurate responding for longer duration, and less accurate responding for briefer duration, target stimuli. No differences in response times were measured. Further experiments revealed that two separate processes produced this complex phenotype: a relatively slowed period of attentional engagement (resulting in compromised detection of fast onset-fast offset stimuli) that only partially masks a generally more accurate pattern of responding. These results, taken with earlier data, indicate that vasopressin plays a critical role in regulating visual attention and cognition, either directly, or via early alterations in neurodevelopment.

Assessment of attention in male and female Brattleboro rats using a self-paced five-choice serial reaction time task

“…Clearly, more research is needed to assess how sex b r a i n r e s e a r c h 1 5 3 7 ( 2 0 1 3 ) 1 7 4 -1 7 9 differences may interact with vasopressin to account for potential behavioral or cognitive effects. The studies conducted by Jentsch et al (2003) and Jentsch (2003), which used a lateralized reaction time task (see the Introduction section) in male rats, provide the closest comparisons possible with the present study's findings. In the study by Jentsch (2003), HZ rats failed to exhibit differences in choice accuracy at 30, 5, and 2.5 s durations but displayed improved choice accuracy at a 1 s duration.…”

“…In the study by Jentsch (2003), HZ rats failed to exhibit differences in choice accuracy at 30, 5, and 2.5 s durations but displayed improved choice accuracy at a 1 s duration. In another lateralized reaction time study, Jentsch et al (2003) reported that BRAT rats showed improved choice accuracy at a 2.0 s duration but displayed impaired choice accuracy at a 0.2 s duration. Considering these findings together, Jentsch et al (2003) suggested that increases in vasopressinergic tone may diminish attention accuracy.…”

“…In another lateralized reaction time study, Jentsch et al (2003) reported that BRAT rats showed improved choice accuracy at a 2.0 s duration but displayed impaired choice accuracy at a 0.2 s duration. Considering these findings together, Jentsch et al (2003) suggested that increases in vasopressinergic tone may diminish attention accuracy. The present findings fail to support these conclusions, since accuracy differences were not observed in male BRAT or HZ rats compared to LE rats, and that deficits, rather than improvements, in attention accuracy were observed in female BRAT rats.…”

Effects of atomoxetine and methylphenidate on performance of a lateralized reaction time task in rats

“…After being trained to make the sustained nose poke, rats began daily testing on the lateralized reaction time task (Brown and Robbins 1989;Carli et al 1985;Jentsch et al 2003); in the first four sessions, a target stimulus of fixed duration was presented for all trials in a session (which terminated after 60 min or 128 trials, whichever came first). The task began with the illumination of the house light and the rats retrieving a single pellet from the magazine.…”

“…In this task, rats engage in a variable-duration fixation response while waiting for the delivery of a visual target in the left or right visual fields (Brown and Robbins 1989;Carli et al 1985;Jentsch et al 2003). During this fixation response, rats must divide and orient their attention, monitoring both locations for the stimulus delivery; because the temporal onset and duration and spatial localization of the target are unknown to the rats, the subjects will "miss" the target if they attend to only one location and/or fail to sustain their attention.…”