Elsevier

Biological Psychiatry

Volume 62, Issue 6, 15 September 2007, Pages 687-693
Biological Psychiatry

Original Article
Sensitivity of the Five-Choice Serial Reaction Time Task to the Effects of Various Psychotropic Drugs in Sprague-Dawley Rats

https://doi.org/10.1016/j.biopsych.2006.11.017Get rights and content

Background

Attentional deficits accompany many psychiatric disorders, underscoring the need for rodent models of attention to screen novel therapeutic agents and characterize the biological basis of attention. The five-choice serial reaction time task (5CSRTT) is one such model. Here, we characterized the effects of four standard psychotropic agents on performance in the 5CSRTT.

Methods

Male Sprague-Dawley rats were trained in the 5CSRTT (5-sec inter-trial interval and .5-sec stimulus duration) until they reliably performed at > 60% accuracy and < 20% omissions. They were then treated systemically with the stimulant methylphenidate (MPH) (.063–2.0 mg/kg), the N-methyl-D-aspartate antagonist dizocilpine (MK-801) (.008–.25 mg/kg), the norepinephrine reuptake inhibitor desipramine (DMI) (.63–10 mg/kg), or the κ-receptor agonist U69,593 (.25–2.0 mg/kg) 30 min before testing.

Results

Methylphenidate (.5 mg/kg) increased accuracy. Dizocilpine impaired accuracy (.25 mg/kg), increased premature responses (.063–.25 mg/kg), and increased omissions (.25 mg/kg). Desipramine decreased premature responses (5.0 mg/kg) but increased omissions (10 mg/kg), correct response latencies (5.0–10.0 mg/kg), and reward latencies (5.0–10.0 mg/kg). The κ-opioid agonist U69,593 (1.0–2.0 mg/kg) increased omissions and correct response latencies.

Conclusions

In Sprague-Dawley rats, psychotropic drugs with distinct pharmacological profiles produced distinguishable effects in the 5CSRTT. The effects of these classes of drugs under our testing conditions are qualitatively similar to their effects in humans.

Section snippets

Rats

Sixteen male Sprague-Dawley rats (Charles River, Durham, North Carolina; 250–300 g at the start of the experiment) were housed in pairs in clear Plexiglas cages on a 12-hour/12-hour light-dark cycle (lights on at 7:00 am). Rats were given 1 week to acclimate to the housing conditions with free access to food (Purina Rat Chow; Ralston Purina, St. Louis, Missouri) and water. Twenty-four hours before the onset of training and throughout training, rats were food-restricted to 85% of their

Results

The figures illustrate the effects of MPH, MK-801, DMI, and U69,593 on attentional accuracy, omissions, and premature responses. Correct response latency and latency to collect food rewards (reward latency) are listed in Table 1. Methylphenidate (Figure 1;Table 1) affected accuracy [F(6,36) = 3.09, p < .05]: it increased accuracy relative to vehicle at .5 mg/kg (p < .05, Bonferroni tests). Methylphenidate did not affect any other performance measure.

Dizocilpine (Figure 2;Table 1) affected

Discussion

The current experiment was designed to examine the acute effects of four pharmacologically distinct drugs on the performance of Sprague-Dawley rats in the 5CSRTT. To date, the majority of research using this model has been performed with either Lister or Long-Evans (hooded) rats (e.g., Carli et al 1983, Cole and Robbins 1989, McGaughty et al 2002). We tested Sprague-Dawley rats because this strain has been used in the majority of our previous research on the molecular basis of addiction and

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