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

Alvin V Terry, Jerry J. Buccafusco, R. Foster Schade, Leah Vandenhuerk, Patrick Michael Callahan, Wayne D. Beck, Elizabeth J. Hutchings, James M. Chapman, Pei Li, Michael G. Bartlett

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)941-951
Number of pages11
JournalBiochemical Pharmacology
Volume83
Issue number7
DOIs
StatePublished - Apr 1 2012

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Cotinine
Excitatory Amino Acid Antagonists
N-Methylaspartate
Metabolites
Nicotine
Reaction Time
Rats
Glutamic Acid
Dizocilpine Maleate
Pharmacology
Startle Reflex
Compulsive Behavior
Impulsive Behavior
Glutamate Receptors
Short-Term Memory
Drinking Water
Primates
Oral Administration
Half-Life
Data storage equipment

Keywords

  • Attention
  • Compulsivity
  • Impulsivity
  • Nicotinic
  • Schizophrenia

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

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. / Terry, Alvin V; Buccafusco, Jerry J.; Schade, R. Foster; Vandenhuerk, Leah; Callahan, Patrick Michael; Beck, Wayne D.; Hutchings, Elizabeth J.; Chapman, James M.; Li, Pei; Bartlett, Michael G.

In: Biochemical Pharmacology, Vol. 83, No. 7, 01.04.2012, p. 941-951.

Research output: Contribution to journalArticle

Terry, Alvin V ; Buccafusco, Jerry J. ; Schade, R. Foster ; Vandenhuerk, Leah ; Callahan, Patrick Michael ; Beck, Wayne D. ; Hutchings, Elizabeth J. ; Chapman, James M. ; Li, Pei ; Bartlett, Michael G. / 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. In: Biochemical Pharmacology. 2012 ; Vol. 83, No. 7. pp. 941-951.
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AU - Buccafusco, Jerry J.

AU - Schade, R. Foster

AU - Vandenhuerk, Leah

AU - Callahan, Patrick Michael

AU - Beck, Wayne D.

AU - Hutchings, Elizabeth J.

AU - Chapman, James M.

AU - Li, Pei

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