Abstract
Stimulant psychosis and addiction are most commonly associated with repeated, high-dose binges or runs, typically preceded by a more intermittent pattern of stimulant abuse. We previously reported that rats exposed to an escalating dose-run pattern of amphetamine administration exhibited changes in their behavioral response profile that differed both qualitatively and quantitatively from the response to either acute or intermittent daily treatment. To determine the generality of these effects and characterize further the nature of the behavioral and neurochemical changes of this treatment, rats received single daily injections of amphetamine (2.5 or 4.0 mg/kg s.c.) or equimolar doses of methamphetamine, followed by multiple runs (four daily injections at 2-hr intervals) with the pretreatment dose. This treatment resulted in a unique behavioral profile, including a profound increase in the relative expression of locomotion vs.stereotypy. The markedly enhanced poststereotypy locomotor activation was characterized by repeated “burst”-like episodes of ambulation. The number of runs required for the emergence of this behavior was dose dependent and was similar for the two drugs except that with methamphetamine, there also was a marked prolongation of the poststereotypy locomotor response during run exposures. During runs, both drugs produced a decline in the caudate but not the nucleus accumbens microdialysate dopamine response, whereas only methamphetamine produced a decline in the serotonin response that was apparent in both regions. The possible relationship between these behavioral and neurochemical changes and their implications for high dose patterns of stimulant abuse are discussed.
Footnotes
-
Send reprint requests to: Dr. David S. Segal, Psychiatry Department (0603), UCSD School of Medicine, La Jolla, CA 92093.
-
↵1 This work was supported in part by United States Public Health Service Grants DA-01568 and DA-04157. D.S.S. is the recipient of United States Public Health Service NIMH Career Scientist Award MH-70183.
-
↵2 D. S. Segal and R. Kuczenski, unpublished observations.
- Abbreviations:
- AMPH
- amphetamine
- METH
- methamphetamine
- DA
- dopamine
- NE
- norepinephrine
- 5-HT
- serotonin
- SDI
- single daily injection(s)
- ICI
- intercrossover interval
- ANOVA
- analysis of variance
- AUC
- area under the curve
- Received November 20, 1996.
- Accepted April 15, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|