Multiple within-day conflict testing to define the time course of anxiolytic drug effects.
The present article describes a method for multiple within-day conflict testing to conduct drug treatment time course studies more efficiently. Groups of female Sprague-Dawley rats were trained for conflict testing in a standard one-session/day procedure [conditioned suppression of drinking (CSD)]. In this task, thirsty rats (24 h water-restricted) drink from a tube that is electrified only when a tone is on (approximately 20% of the 10-min session time). In Experiment 1 it was found that there was no significant variation in CSD conflict behavior when subjects were tested at 0600, 1200, or 1800 h using the traditional procedure of one test/day. In Experiment 2, subjects were assigned to treatment groups such that there were three 5-min test sessions per day and the test-retest interval was either 2, 4, or 6 h (centered around 1200 h). Test-retest intervals of 6 h (i.e., tests at 0600, 1200, and 1800 h) resulted in comparable levels of punished responding across the repeated within-day tests, whereas test-retest intervals of 2 h and, to a lesser extent 4 h, resulted in unequal within-day conflict behavior characterized by a greater number of shocks accepted and a greater volume of water consumed during the earliest test periods each day. In another group of rats, it was determined that conflict behavior sampled five times/day in 3-min sessions separated by a 3-h test-retest interval (i.e., tests at 0600, 0900, 1200, 1500, and 1800 h) also resulted in stable conflict behavior across the various within-day test periods. In Experiment 3, it was found that acute IP challenges with anticonflict treatments that exhibit either a long duration of action (phenobarbital: 40 mg/kg) or a significant delay to onset in addition to a long duration (MK-801: 0.20 mg/kg) yielded time course data comparable to those obtained using the traditional one test/day procedure. These findings indicate that the use of multiple within-day conflict testing can greatly increase the efficiency of these procedures, particularly when drug treatment timecourse information is desired.
Commissaris
R L
RL
Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48202, USA.
Xie
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Z
Ninichuk
P J
PJ
Markovska
V L
VL
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D003220:Conflict, Psychological; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004327:Drinking Behavior / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014151:Anti-Anxiety Agents; D018691:Excitatory Amino Acid Antagonists; D006993:Hypnotics and Sedatives; D016291:Dizocilpine Maleate; D010634:Phenobarbital