Disruption of sensitization to methylphenidate by a single administration of MK-801.
Blockade of sensitization to methylphenidate by a single injection of MK-801 was investigated using a computerized activity monitoring system. Male Sprague-Dawley rats were housed in test cages and motor activity was recorded continuously for 16 days. After 2 days of baseline recording and a saline injection on day 3, the rats were randomly divided into four experimental groups. All received 2.5 mg/kg of methylphenidate (s.c.) once a day from days 4 to 9, then after five days of no treatment, they were re-challenged with 2.5 mg/kg of methylphenidate on day 15. One group received only methylphenidate, while the other three groups also received a single i.p. injection of MK-801 (0.30 mg/kg) either 24 h (day 3) or 1 h prior to the first of the six methylphenidate injections (day 4), or 1 h prior to the second methylphenidate injection (day 5). A single injection of MK-801 on day 4 (1 h prior to methylphenidate) blocked the development of sensitization to methylphenidate, since a sensitized response could not be elicited six days after cessation of repeated methylphenidate administration (day 15). However, sensitization to methylphenidate still occurred in the groups receiving MK-801 (0.30 mg/kg) on day 5, indicating that the mechanism by which a single injection of MK-801 disrupts sensitization to methylphenidate is sensitive to timing and is not a direct long-term effect. In conclusion, a single injection of MK-801 persistently blocks the development of sensitization to methylphenidate only if it is given with methylphenidate on the first day of the repetitive treatment phase.
Gaytan
Osvaldo
O
Department of Neurobiology and Anatomy, The University of Texas Health Science Center at Houston, 77030, USA.
Swann
Alan C
AC
Dafny
Nachum
N
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013239:Stereotyped Behavior / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D008774:Methylphenidate; D016291:Dizocilpine Maleate