Long-term voluntary D-amphetamine consumption and behavioral predictors for subsequent D-amphetamine addiction in rats.

Flexibility of drug taking is characteristic for "controlled" drug consumption whereas addiction is reflected by inflexibility and persistent high risk to relapse. Male Wistar rats (N = 12) that were given a continuous free choice between water and D-amphetamine solutions for 16 weeks, revealed a moderate and flexible pattern of D-amphetamine intake when tested again after 36 weeks of drug deprivation. A second group of rats had the same choice between water and D-amphetamine for 42 weeks. In the retest after abstinence, six out of 12 rats showed a moderate and flexible pattern of intake whereas the other animals revealed an excessively high and inflexible D-amphetamine consumption. They took high doses despite an adverse bitter taste of the drug solutions caused by addition of quinine. After 39 weeks of moderate D-amphetamine intake in the long-term period exactly the same animals had spontaneously and suddenly increased their D-amphetamine consumption. In a retrospective view, the later inflexible D-amphetamine consumers had already shown differences to their flexible conspecifics before their first drug access. During "tetradic" encounter tests the later "inflexible" animals were more interested in non-social stimuli than the later "flexible" ones. The results are discussed in respect to predisposition factors that might facilitate or inhibit the development of loss of control over drug intake.