Chromium picolinate reduces morphine-dependence in rats, while increasing brain serotonin levels

Chromium is an essential trace element with anti-diabetic and anti-depressant effect; the latter is considered related to chromium properties of increasing brain serotonin. Cr³⁺ salts were shown to improve some forced swimming-parameters and to induce rewarding effects, which are additive to those of morphine, but Cr effect on addictive processes has not been tested.

The present study aimed to assess chromium picolinate (CrPi) influence on morphine-dependence in rats.

We used five groups of 10 rats. Groups 1 and 2 (controls) received saline, respectively CrPi, 0.01 mg/kg/day, for 10 days. In groups 3, 4 and 5 dependence was induced with progressively-increased morphine doses (from 5 - day 1-90 mg/kg/day - day 10, s.c.). Group 3 received only morphine, while groups 4 and 5 received CrPi, i.p., 10 and respectively 5 μg/kg/day, during the 10 days of dependence induction. On day 11, groups 3, 4, and 5 were administered 90 mg/kg morphine, and, 2 h later, all rats received naloxone, 2 mg/kg s.c., to precipitate withdrawal. We compared withdrawal intensity in group 3 vs. groups 4 and 5, assessing both individual symptoms and Gellert-Holtzman global withdrawal score. Upon rats sacrifice at the end of the experiments, brain serotonin (5HT) in certain areas and serum Cr were assessed.

Some withdrawal signs were unequally influenced by CrPi: compulsive mastication was reduced by both CrPi doses (p < 0.05), while teeth chattering and grooming were significantly reduced only by the higher dose (p < 0.05). Withdrawal score was reduced by both CrPi doses: from 132.4 ± 9.87 - group 3 to 122.2 ± 6.47 - group 4 (p < 0.01 vs. group 3) and 124.1 ± 8.41 - group 5 (p < 0.05 vs. group 3). CrPi reduction of withdrawal is accompanied by increased brain 5 H T, mainly in the prefrontal cortex (646.3 ± 8.51 - group 3 vs. 661.5 ± 14.63 - group 4, p < 0.01 and 660.7 ± 14.01 pg/mg tissue - group 5, p < 0.05 vs. group 3). CrPi also increases brain 5 H T in non-dependent rats (prefrontal cortex: 541.6 ± 31.80, group 1 and 565.5 ± 16. 46 pg/mg tissue, group 2, p < 0.05). Administration of CrPi determined a dose-dependent increase of serum Cr.

Our study evidenced a slight, but significant reduction of morphine dependence in rats induced by chromium picolinate, accompanied by increased brain serotonin. This might be considered a supplementary evidence for chromium anti-depressant effect and its serotonin-mediated mechanisms.