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Basic Clin Pharmacol Toxicol ; 110(4): 347-52, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22004516

ABSTRACT

Prolonged consumption of ethanol produces prefrontal cortex (PFC) dysfunction in patients, and this has been demonstrated using structural, physiological and psychological measurements. We therefore wanted to develop an animal model of PFC dysfunction to study whether this state changes sensitivity for ethanol or other behavioural/motivational measures. Adolescent Wistar rats were first screened in the novel object recognition task to establish a pre-treatment baseline measure of locomotor activity, anxiety-like behaviour and PFC function. Animals were divided into four treatment groups [saline, 5 mg/kg phencyclidine (PCP), 2.5g/kg ethanol, ethanol + PCP] and injected i.p. for 5 days followed by a 2-day washout. On the 8th day, animals were allowed to explore a Y-maze for 10 min. and spontaneous alternations were recorded using the ANY-maze tracking system. PCP, a classic drug used to induce PFC dysfunction in animals, did not significantly reduce the % correct alternations relative to the 70% level achieved by the saline group. Ethanol and the combination of Ethanol + PCP, however, significantly reduced alternations to approximately 30%. The combined dose was not additive in terms of Y-maze impairment, and these animals had less total distance travelled and greater time immobile relative to the other groups. We therefore concluded that injection of 2.5 g/kg ethanol for 5 days in Wistar rats produces a more substantial, consistent and valid PFC dysfunction than 5 mg/kg PCP.


Subject(s)
Behavior, Animal/drug effects , Ethanol/toxicity , Maze Learning/drug effects , Phencyclidine/toxicity , Animals , Disease Models, Animal , Drug Administration Schedule , Ethanol/administration & dosage , Hallucinogens/administration & dosage , Hallucinogens/toxicity , Male , Motor Activity/drug effects , Phencyclidine/administration & dosage , Prefrontal Cortex/drug effects , Prefrontal Cortex/pathology , Rats , Rats, Wistar
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