Acute sensitivity of FAST and SLOW mice to the effects of abused drugs on locomotor activity

Tamara Phillips, S. Burkhart-Kasch, C. C. Gwiazdon, John Jr Crabbe

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The universal nature of the stimulant or euphoric effect of addictive drugs suggests that it may be an important predictor of a drug's addiction potential. Furthermore, assessment of stimulant sensitivity could be useful for predicting the liability of individuals to drug abuse. The stimulant actions of abused drugs from different pharmacological classes may share a common biological mechanism. We investigated this notion by assessing the drug responses relative to base-line locomotor activity of mice selectively bred for increased (FAST) and reduced (SLOW) sensitivity to ethanol-induced stimulation. FAST mice were more sensitive than SLOW mice to the stimulant effects of methanol (1.5-3.0 g/kg), t-butanol (0.2-0.6 g/kg), n-propanol (0.15-1.2 g/kg), pentobarbital (10-40 mg/kg) and phenobarbital (15-120 mg/kg). FAST and SLOW mice were similarly stimulated by d-amphetamine (1.25- 10 mg/kg) and caffeine (2.5-20 mg/kg). The activity of FAST and SLOW mice was equally depressed by nicotine (0.5-2.0 mg/kg) and morphine (4-75 mg/kg). Finally, FAST mice were unaffected, whereas SLOW mice were depressed by diazepam (1-8 mg/kg). Selection for relative sensitivity to stimulation by ethanol has generalized to other alcohols and to barbiturates, but not to several other abused drugs, including amphetamine. The data presented here support a hypothesized common mechanism of stimulant action for alcohols and barbiturates, and suggest that differences in sensitivity to drug stimulant effects can be seen in the absence of dopamine system differences.

Original languageEnglish (US)
Pages (from-to)525-533
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume261
Issue number2
StatePublished - 1992
Externally publishedYes

Fingerprint

Locomotion
Pharmaceutical Preparations
Barbiturates
Substance-Related Disorders
Ethanol
Alcohols
tert-Butyl Alcohol
1-Propanol
Dextroamphetamine
Amphetamine
Pentobarbital
Phenobarbital
Diazepam
Caffeine
Nicotine
Morphine
Methanol
Dopamine
Pharmacology

ASJC Scopus subject areas

  • Pharmacology

Cite this

Acute sensitivity of FAST and SLOW mice to the effects of abused drugs on locomotor activity. / Phillips, Tamara; Burkhart-Kasch, S.; Gwiazdon, C. C.; Crabbe, John Jr.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 261, No. 2, 1992, p. 525-533.

Research output: Contribution to journalArticle

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