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Volume 16, Number 23, Issue of December 1, 1996 pp. 7670-7677
Copyright ©1996 Society for Neuroscience

Effects of Binge Pattern Cocaine Administration on Dopamine D₁ and D₂ Receptors in the Rat Brain: An In Vivo Study Using Positron Emission Tomography

Received April 17, 1996; revised Aug. 9, 1996; accepted Sept. 5, 1996.

Hideo Tsukada¹, Jason Kreuter², Christopher E. Maggos², Ellen M. Unterwald^{2, 3}, Takeharu Kakiuchi¹, Shingo Nishiyama¹, Masami Futatsubashi¹, and Mary Jeanne Kreek²

¹ Central Research Laboratory, Hamamatsu Photonics K. K., Shizuoka 434, Japan, ² Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, New York 10021, and ³ Department of Psychiatry, New York University Medical Center, New York, New York 10003

The aim of the present study was to determine the effect of "binge" pattern cocaine administration on dopamine D₁ and D₂ receptors in the rat brain. Male Sprague Dawley rats were injected three times at 1 hr intervals with saline or cocaine (15 mg/kg) each day for 2, 7, or 14 d. The in vivo binding of [¹¹C]SCH23390 (dopamine D₁ receptor antagonist) and [¹¹C]N-methylspiperone (NMSP; dopamine D₂ receptor antagonist) in the striatal region was measured by a high-resolution positron emission tomography at 1 and 3.5 hr, respectively, after the last cocaine or saline injection. Acute (2 d) binge cocaine administration did not change the in vivo binding potential of [¹¹C]SCH23390 or the binding of [¹¹C]NMSP in the striatum. After 7 d of binge cocaine administration, a significant decrease in the binding potential of [¹¹C]SCH23390 was observed, whereas no change in the binding of [¹¹C]NMSP was found. After 14 d of binge cocaine administration, the in vivo binding was significantly reduced for both [¹¹C]SCH23390 and [¹¹C]NMSP. Separate saturation experiments indicated that the observed alterations of in vivo binding were attributable mainly to apparent alterations in the affinity and not the number of binding sites. These results suggest that both dopamine D₁ and D₂ receptors may have altered physiologically available binding sites after binge pattern cocaine administration.

Key words: cocaine; dopamine receptors; [¹¹C]SCH23390; [¹¹C]N-methylspiperone; positron emission tomography; rat brain

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