PharmacologyBiochemistry&Behavior, Vol. 22, pp. 901-903, 1985. © AnkhoInternationalInc. Printed in the U.S.A. 0091-3057/85$3,00 + .00 BRIEF COMMUNICATION Sensitization of Rotational Behavior Produced by a Single Exposure to Cocaine GUAN LIN-CHU,* TERRY E. ROBINSONt I bND JILL B. BECKER~" *Institute of Psychology, Academia Sinica, Be~iing, The People's Republic of China and tPsychology Department, The University of Michigan, Ann Arbor, MI 48104-1687 Received 25 June 1984 LIN-CHU, G., T. E. ROBINSON AND J. B. BECKER. Sensitization of rotational behavior produced by a single exposure to cocaine. PHARMACOL BIOCHEM BEHAV 22(5)901-903, 1985.--In rats with a unilateral 6-OHDA lesion of the substantia nigra a single exposure to cocaine significantly enhanced the ipsiversive rotational behavior produced by a second injection given one week later. It is concluded that it is not necessary to repeatedly administer psychomotor stimulant drugs to produce long-lasting changes in brain and behavior. Cocaine Rotational behavior Sensitization Reverse tolerance 6-Hydroxydopamine THE repeated administration of psychomotor stimulant drugs produces a longqasting facilitation in the behavioral responsiveness to subsequent injections. For example, the locomotion, stereotypy or rotational behavior produced by amphetamine (AMPH) appears more rapidly, is more intense and/or is more persistent if animals have been previously exposed to AMPH ([4, 8, 10, 18], see [19] for review). This phenomenon of "reverse tolerance," or behavioral sensiti- zation, is thought to provide an animal analogue of stimulant-induced psychosis in humans [12,19]. In many studies relatively high doses of dopamine-mimetic drugs are administered daily for long periods of time to produce behav- ioral sensitization. However, aggressive drug regimens may not be necessary to produce behavioral sensitization. For example, previous studies have shown that a single injection of AMPH enhances both rotational behavior and AMPH- stimulated striatal dopamine release [ 13,16]. The experiment reported here was conducted to determine if a single injec- tion of another stimulant, cocaine, could also produce a long-lasting sensitization of rotational behavior. METHOD Female Holtzman rats weighing 200-300 g received an injection of 6-hydroxydopamine hydrobromide (8 /~g/4 /~l) into the right rostrai zona compacta of the substantia nigra 30 min following pretreatment with desipramine [2]. After at least 5 weeks of recovery from surgery the rats received an IP injection of either 0.9% saline (n= 16), 10 mg/kg of cocaine hydrochloride (n--8) or 40 mg/kg of cocaine (n--10), then were placed in automated spherical rotometers and rota- tional behavior recorded for 1 hr (see [16]). One week after this initial experience all animals received a second injection of cocaine, and rotational behavior was recorded again. Dur- ing this second test session half the saline-pretreated rats received 10 mg/kg and half 40 mg/kg of cocaine, and the cocaine-pretreated rats received the same dose of cocaine they were pretreated with. These doses of cocaine were cho- sen because: (1) Stripling and Ellinwood [20] reported that 40 mg/kg of cocaine produced more reliable sensitization of stereotyped belaavior than 20 mg/kg; and (2) Heikkila et al. [6] found that 20 mg/kg of cocaine resulted in levels of rota- tional behavior comparable to that produced by 1.0 mg/kg of AMPH. Therefore, these doses appeared to span the range necessary to produce both rotational behavior and sensitiza- tion. At least one week after the last test session all animals were decapitated, the striatum removed, and assayed for dopamine using high performance liquid chromatography with electrochemical detection (see [16]). RESULTS Only rats that had at least an 85% depletion of right striatal dopamine and turned ipsiversive when given cocaine were included in the folowing analysis (mean dopamine de- pletion +-S.E.M. -- 96.9-+1.14%). This was done to reduce variation in rotation rate due to variation in (1) the size of the lesion, and (2) the side of the lesion, relative to the "domi- nant" hemisphere for rotational behavior [14]. Unfortu- nately, the rats could not be screened to determine the "dominant" hemisphere prior to the 6-OHDA lesion, as suggested by Robinson and Becker [14], because this would "presensitize" them. Approximately 15% of the animals 1Requests for reprints should be addressed to Dr. Terry E. Robinson, Neuroscience Laboratory Building, The University of Michigan, 1103 E. Huron St., Ann Arbor, MI 48104-1687. 901