PT  - JOURNAL ARTICLE
AU  - Elizabeth J. Hutchings
AU  - Jennifer L. Waller
AU  - Alvin V. Terry, Jr.
TI  - Differential Long-Term Effects of Haloperidol and Risperidone on the Acquisition and Performance of Tasks of Spatial Working and Short-Term Memory and Sustained Attention in Rats
AID  - 10.1124/jpet.113.209031
DP  - 2013 Dec 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 547--556
VI  - 347
IP  - 3
4099  - http://jpet.aspetjournals.org/content/347/3/547.short
4100  - http://jpet.aspetjournals.org/content/347/3/547.full
SO  - J Pharmacol Exp Ther2013 Dec 01; 347
AB  - A common feature of the neuropsychiatric disorders for which antipsychotic drugs are prescribed is cognitive dysfunction, yet the effects of long-term antipsychotic treatment on cognition are largely unknown. In the current study, we evaluated the effects of long-term oral treatment with the first-generation antipsychotic haloperidol (1.0 and 2.0 mg/kg daily) and the second-generation antipsychotic risperidone (1.25 and 2.5 mg/kg daily) on the acquisition and performance of two radial-arm maze (RAM) tasks and a five-choice serial reaction-time task (5C-SRTT) in rats during days 15–60 and 84–320 days of treatment, respectively. In the RAM, neither antipsychotic significantly affected the acquisition or performance of a spatial win shift or a delayed non–match-to-position task. Conversely, in the rats administered 5C-SRTT, haloperidol was associated with profound deficits in performance, and the subjects were not able to progress through all stages of task acquisition. Depending on the dose, risperidone was associated with a greater number of trials to meet specific performance criteria during task acquisition compared with vehicle-treated controls; however, most subjects were eventually able to achieve all levels of task acquisition. Both haloperidol and risperidone also increased the number of perseverative and time-out responses during certain stages of task acquisition, and the response and reward latencies were slightly higher than controls during several stages of the study. These results in rats suggest that while long-term treatment with haloperidol or risperidone may not significantly affect spatial working or short-term memory, both antipsychotics can (depending on dose) impair sustained attention, decrease psychomotor speed, increase compulsive-type behaviors, and impair cognitive flexibility.