TY - JOUR
T1 - The nicotine metabolite, cotinine, attenuates glutamate (NMDA) antagonist-related effects on the performance of the five choice serial reaction time task (5C-SRTT) in rats
AU - Terry, Alvin V.
AU - Buccafusco, Jerry J.
AU - Schade, R. Foster
AU - Vandenhuerk, Leah
AU - Callahan, Patrick M.
AU - Beck, Wayne D.
AU - Hutchings, Elizabeth J.
AU - Chapman, James M.
AU - Li, Pei
AU - Bartlett, Michael G.
N1 - Funding Information:
The authors would like to thank Ms. Ashley Davis for her administrative assistance in preparing this article and Ms. Samantha Warner and Ms. Kristy Bouchard for technical assistance. This work was supported by the National Institute of Aging/National Institutes of Health ( AG032140 ).
PY - 2012/4/1
Y1 - 2012/4/1
N2 - Cotinine, the most predominant metabolite of nicotine in mammalian species, has a pharmacological half-life that greatly exceeds its precursor. However, until recently, relatively few studies had been conducted to systematically characterize the behavioral pharmacology of cotinine. Our previous work indicated that cotinine improves prepulse inhibition of the auditory startle response in rats in pharmacological impairment models and that it improves working memory in non-human primates. Here we tested the hypothesis that cotinine improves sustained attention in rats and attenuates behavioral alterations induced by the glutamate (NMDA) antagonist MK-801. The effects of acute subcutaneous (dose range 0.03-10.0 mg/kg) and chronic oral administration (2.0 mg/kg/day in drinking water) of cotinine were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a five choice serial reaction time task (5C-SRTT). The results indicated only subtle effects of acute cotinine (administered alone) on performance of the 5C-SRTT (e.g., decreases in timeout responses). However, depending on dose, acute treatment with cotinine attenuated MK-801-related impairments in accuracy and elevations in timeout responses, and it increased the number of completed trials. Moreover, chronic cotinine attenuated MK-801-related impairments in accuracy and it reduced premature and timeout responses when the demands of the task were increased (i.e., by presenting VSDs or VITIs in addition to administering MK-801). These data suggest that cotinine may represent a prototype for compounds that have therapeutic potential for neuropsychiatric disorders (i.e., by improving sustained attention and decreasing impulsive and compulsive behaviors), especially those characterized by glutamate receptor alterations.
AB - Cotinine, the most predominant metabolite of nicotine in mammalian species, has a pharmacological half-life that greatly exceeds its precursor. However, until recently, relatively few studies had been conducted to systematically characterize the behavioral pharmacology of cotinine. Our previous work indicated that cotinine improves prepulse inhibition of the auditory startle response in rats in pharmacological impairment models and that it improves working memory in non-human primates. Here we tested the hypothesis that cotinine improves sustained attention in rats and attenuates behavioral alterations induced by the glutamate (NMDA) antagonist MK-801. The effects of acute subcutaneous (dose range 0.03-10.0 mg/kg) and chronic oral administration (2.0 mg/kg/day in drinking water) of cotinine were evaluated in fixed and variable stimulus duration (VSD) as well as variable intertrial interval (VITI) versions of a five choice serial reaction time task (5C-SRTT). The results indicated only subtle effects of acute cotinine (administered alone) on performance of the 5C-SRTT (e.g., decreases in timeout responses). However, depending on dose, acute treatment with cotinine attenuated MK-801-related impairments in accuracy and elevations in timeout responses, and it increased the number of completed trials. Moreover, chronic cotinine attenuated MK-801-related impairments in accuracy and it reduced premature and timeout responses when the demands of the task were increased (i.e., by presenting VSDs or VITIs in addition to administering MK-801). These data suggest that cotinine may represent a prototype for compounds that have therapeutic potential for neuropsychiatric disorders (i.e., by improving sustained attention and decreasing impulsive and compulsive behaviors), especially those characterized by glutamate receptor alterations.
KW - Attention
KW - Compulsivity
KW - Impulsivity
KW - Nicotinic
KW - Schizophrenia
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U2 - 10.1016/j.bcp.2011.12.043
DO - 10.1016/j.bcp.2011.12.043
M3 - Article
C2 - 22244928
AN - SCOPUS:84857361348
SN - 0006-2952
VL - 83
SP - 941
EP - 951
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 7
ER -