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One group of rats (n equals 6) was allowed free access to food combined with morphine and cocaine for 3 weeks, another group combined with either morphine or cocaine alone for 3 weeks. Intensity of decrease in body weight by withdrawal and ratios of spontaneous morphine and cocaine intake were compared, and the cross-spontaneous drug intake between morphine and cocaine using cocaine and morphine dependent rats was investigated, respectively. The results indicate that (a) decreased rate in body weight by withdrawal after 3 weeks administration with morphine-cocaine mixtures increased slightly, and spontaneous intake ratio for the higher drug-admixed food during administration period was also slightly increased as compared with a morphine added diet alone.  (b) However, spontaneous intake ratio of both morphine [morphine (1 mg/g of food) vs. a normal diet (N.D.)] and cocaine [cocaine (2 mg/g of food) vs. N.D] increased 30 and 50 approximately 60% respectively, and these changes were maintained for about two months. (c) Spontaneous cocaine intake ratio after 3 weeks administration of morphine was almost the same level as that in cocaine dependent rats and decreased dependently when the administration period was extended. Spontaneous morphine intake ratio after 3 weeks administration of cocaine was 20% lower in total daily intake ratio as compared to morphine dependent rats, but spontaneous morphine intake ratio as compared to morphine dependent rats was gradually increased as in morphine dependent rats. (d) Furthermore, morphine-quinine combined treatment and cocaine or codeine treatment had no effect on spontaneous intake of quinine. These data suggest that combinations of morphine and cocaine have promoting properties of morphine and cocaine intake, respectively. Cross-spontaneous drug intake between morphine and cocaine was successful only in cocaine dependent rats using this method.

Dependence on and preference for morphine in rats (III). Improvement of spontaneous drug intake after morphine-cocaine combined treatment