We have introduced a rat model of cocaine withdrawal syndrome. Rats were addicted to cocaine by continuous osmotic pump infusion, the pumps were removed, and the spontaneous behaviors of the rats were quantified. These behaviors are similar to ones shown by rats in nicotine and morphine withdrawal: ptosis, chewing, teeth chattering, gasps, writhes, seminal ejaculations, head shakes and tremors.
|Overall abstinence signs (+/- SEM) as a function of three infusion rates (60, 40 and 0 mg/kg/day cocaine HC1 in saline) and the six observation times following termination of infusion. Note that eight rats per treatment group were observed through 48 h (solid lines), while only four of these per group were also observed at 84 and 156 h (dotted lines). *p < 0.05 vs. saline group over 12-48 h, ** p < 0.01 vs. saline group, and p vs. < 0.05 vs. 40 mg/kg/day group over 12-48 h.|
High infusion rate groups (60 mg/kg) showed significantly more signs than low infusion rate groups (40 mg/kg), which showed significantly more signs than saline infused groups. Cocaine injection reversed withdrawal symptoms. Withdrawal signs peaked 36 to 48 hours after cocaine termination. Longer infusion time (6.5 days) caused more withdrawal symptoms than shorter infusion time (1.5 days).
In other work, we examined the effect of Transcranial Electrostimulation Treatment (TCET), a specific form of electrical current passed through the head, on opioid and neurotransmitter levels in the rat brain. TCET had been shown to induce analgesia, alleviate symptoms of opiate withdrawal and alter nociceptive responses in neurons in the midbrain and hypothalamus of rats. TCET consists of a 10 Hz, charge balanced, 10 microamp current passed for 30 minutes between electrodes place in the ears.
Using high performance liquid chromatography, brain levels of several neurotransmitters and their metabolites were measured in slices from various areas of the brains of TCET and sham treated rats. Levels of NE and DA were significantly higher in the hypothalamic region of TCET treated rats than of control rats. The midbrains of TCET rats contained significantly elevated levels of DA; of the NE metabolite, MHPG; and of 5HT and its metabolite, 5HIAA. Thus TCET appears to cause an increase in the synthesis or release of 5HT, DA AND NE in the midbrain and of DA and 5HT in the hypothalamus.
In the opioid experiment, beta-endorphin-like immunoreactivity was measured in blood plasma taken from rats before, during and after TCET, but no demonstrable effects were observed, perhaps due to the possibility that changes may have occurred in the brain but were not reflected in peripheral blood.
Warner, RL, Hudson-Howard, L, Johnston, CM, Skolnick, M. (1990) Serotonin involvement in analgesia induced by transcranial electrostimulation. Life Sci. 46:1131-1138.
Warner, RL, Johnston, CM, Hamilton, R, Wilson, OB, Skolnick, M. (1994) Transcranial electrostimulation (TCET) effects on rat opioid and neurotransmitter levels. Life Sci. 54(7): 481-490.
Malin, DH, Moon, WD, Moy, ET, Jennings, RE, Warner RL, Wilson, OB. (2000) A rodent model of cocaine abstinence syndrome. Pharmacol. Biochem. Behav. 66(2): 323-328.
Search PubMed for additional articles.