Nicotine-induced changes of brain I2-endorphin

A consensus has emerged that endogenous opioid peptides and their receptors play an important role in the psychoactive properties of nicotine. Although behavioral studies have shown that I2-endorphin contributes to the rewarding and emotional effects of nicotine, whether the drug alters the function of brain endorphinergic neurons is not fully explored. These studies investigated the effect of acute, 1 mg/kg, sc, and chronic, daily injection of 1 mg/kg, sc, for 14 days, administration of free base nicotine on brain I2-endorphin and its precursor proopiomelanocortin (POMC). Acute and chronic treatment with nicotine decreased I2-endorphin content in hypothalamus, the principal site of I2-endorphin producing neurons in the brain, and in the endorphinergic terminal fields in striatum and hippocampus. The acute effect of nicotine on I2-endorphin was reversed by the nicotinic antagonist mecamylamine and the dopamine antagonist haloperidol, indicating pharmacological specificity and involvement of dopamine D2-like receptors. Similar observations were made in prefrontal cortex. POMC mRNA in hypothalamus and prefrontal cortex was unchanged following acute nicotine, but it decreased moderately with chronic treatment. The nicotine treatments had no effect on pituitary and plasma I2-endorphin. Taken together, these results could be interpreted to indicate that nicotine alters the synthesis and release of I2-endorphin in the limbic brain in vivo. Altered endorphinergic function may contribute to the behavioral effects of acute and chronic nicotine treatment and play a role in nicotine addiction.