Transition from moderate to excessive drug intake: Change in hedonic set point

Science

Volumn 282, Issue 5387, 1998, Pages 298-300

  Ahmed, S H ^a   Koob, G F ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

COCAINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG ABUSE; DRUG DEPENDENCE; DRUG EFFECT; DRUG SELF ADMINISTRATION; DRUG USE; NONHUMAN; PRIORITY JOURNAL; RAT;

ANIMALS; BEHAVIOR, ADDICTIVE; COCAINE; COCAINE-RELATED DISORDERS; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG TOLERANCE; MALE; RATS; RATS, WISTAR; REINFORCEMENT (PSYCHOLOGY); TIME FACTORS;

ANIMALIA;

EID: 0032500737     PISSN: 00368075     EISSN: None     Source Type: Journal    
DOI: 10.1126/science.282.5387.298     Document Type: Article

References (28)

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13. The apparatus and the detailed procedures for both intravenous catheterization and self-administration of cocaine are described in S. H. Ahmed and G. F. Koob [Psychopharmacology 132, 289 (1997)]. Briefly, adult male Wistar rats (280 to 330 g) were trained 2 hours per day for 14 days on a fixed-ratio 1: time-out 20-s schedule of cocaine self-administration (250 μg per infusion in a volume of 0.1 ml delivered in 4 s). Two noncontingent infusions of the training dose signaled the start of each session. After a predetermined acquisition criterion was reached (at least 15 self-infusions in 2 hours), subjects were divided into two balanced groups. In one group drug access was reduced to 1 hour per session (ShA group); in the other group drug access time was increased to 6 hours (LgA group). This was continued for 12 sessions performed daily, except when days off were imposed to prevent significant weight loss in LgA rats.
14. Acute tolerance is also incompatible with the stable hourly drug intake observed during the last 5 hours of the 6-hour session.
15. 2,22 = 0.98).
16. Main differences with the first experiment were as follows. First, rats (320 to 460 g) had no prior history of cocaine self-administration but were pretrained to press a lever for food; see S. H. Ahmed and G. F. Koob [Psychopharmacology 132, 289 (1997)]. Second, during the escalation phase, cocaine (250 μg per infusion) was available every other day. Third, no noncontingent infusions were given except on rare occasions when a subject failed to respond during the first 10 min. Finally, some subjects were recatheterized and allowed at least 2 days of recovery (seven ShA rats; six LgA rats).
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22. Previous work has shown that chronic exposure to cocaine can produce tolerance to its reinforcing effects [M. W. Emmett-Oglesby and J. D. Lane, Behav. Pharmacol. 3, 193 (1992); M. W. Emmett-Oglesby et al., Drug Alcohol Depend. 32, 247 (1993)]. Nevertheless, such changes in a dose-effect function may also support a set-point hypothesis.
23. Previous work has shown that chronic exposure to cocaine can produce tolerance to its reinforcing effects [M. W. Emmett-Oglesby and J. D. Lane, Behav. Pharmacol. 3, 193 (1992); M. W. Emmett-Oglesby et al., Drug Alcohol Depend. 32, 247 (1993)]. Nevertheless, such changes in a dose-effect function may also support a set-point hypothesis.
24. Cocaine doses were tested during 3-hour testing sessions every other day between regular self-administration sessions. Doses were tested once in the following order: 250, 31.2, 15.6, 62.5, 125, and 0 μg per infusion. Because rats almost ceased to respond 2 hours after cocaine was replaced by vehicle, only the third hour was considered for analysis. Responding for vehicle was averaged regardless of the experimental group [vehicle responses (mean ± SEM) were 7.33 ± 1.1 and 6.75 ± 1.36 for ShA rats and LgA rats, respectively].
25. After the dose-response study, rats were subjected to 35 days of total abstinence. After abstinence, rats with a patent catheter (six ShA rats and five LgA rats) were reexposed to the initial drug access condition.
26. G. F. Koob and E. J. Nestler, J. Neuropsychiatr. Clin. Neurosci. 9, 482 (1997); E. J. Nestler and G. K. Aghajanian, Science 278, 58 (1997).
27. G. F. Koob and E. J. Nestler, J. Neuropsychiatr. Clin. Neurosci. 9, 482 (1997); E. J. Nestler and G. K. Aghajanian, Science 278, 58 (1997).
28. Supported by National Institute on Drug Abuse grants DA04398 and DA08467 (G.F.K.). We thank R. Lintz and M. Beschen for their invaluable technical assistance; L. Gold, C. Heyser, N. Gracy, A. Markou, L. Parsons, J. Walker, M. Weed, and F. Weiss for their helpful comments on an early version of this manuscript; and M. Arends for correcting the remaining errors. This is publication 11573-NP from The Scripps Research Institute.