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The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats
Michael E. DeBakey VA Medical Center, Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston, TX 77030, USA
* Author to whom correspondence should be addressed.
Received: 20 September 2012; in revised form: 26 October 2012 / Accepted: 8 November 2012 / Published: 13 November 2012
Abstract: Medications that target norepinephrine (NE) neurotransmission alter the behavioral effects of cocaine and may be beneficial for stimulant-use disorders. We showed previously that the short-acting, α1-adrenergic antagonist, prazosin, blocked drug-induced reinstatement of cocaine-seeking in rats and doxazosin (DOX), a longer-acting α1 antagonist blocked cocaine’s subjective effects in cocaine-dependent volunteers. To further characterize DOX as a possible pharmacotherapy for cocaine dependence, we assessed its impact on the development and expression of cocaine-induced locomotor sensitization in rats. Rats (n = 6–8) were administered saline, cocaine (COC, 10 mg/kg) or DOX (0.3 or 1.0 mg/kg) alone or in combination for 5 consecutive days (development). Following 10-days of drug withdrawal, all rats were administered COC and locomotor activity was again assessed (expression). COC increased locomotor activity across days indicative of sensitization. The high dose (1.0 mg/kg), but not the low dose (0.3 mg/kg) of DOX significantly decreased the development and expression of COC sensitization. DOX alone did not differ from saline. These results are consistent with studies showing that α1 receptors are essential for the development and expression of cocaine’s behavioral effects. Results also suggest that blockade of both the development and expression of locomotor sensitization may be important characteristics of possible pharmacotherapies for cocaine dependence in humans.
Keywords: cocaine dependence; psychostimulants; norepinephrine; dopamine; locomotor sensitization
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Haile, C.N.; Hao, Y.; O'Malley, P.W.; Newton, T.F.; Kosten, T.A. The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats. Brain Sci. 2012, 2, 619-633.
Haile CN, Hao Y, O'Malley PW, Newton TF, Kosten TA. The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats. Brain Sciences. 2012; 2(4):619-633.
Haile, Colin N.; Hao, Yanli; O'Malley, Patrick W.; Newton, Thomas F.; Kosten, Therese A. 2012. "The α1 Antagonist Doxazosin Alters the Behavioral Effects of Cocaine in Rats." Brain Sci. 2, no. 4: 619-633.