Agmatine also dose-dependently alleviated both thermal and mechanical hyperalgesia symptoms in alcohol-dependent rats. In mice and female rats, this efficacy did not extend to sucrose drinking, indicating some selectivity for ethanol reinforcement. Agmatine reduced alcohol drinking in a dose-dependent fashion, with somewhat greater selectivity in alcohol-dependent female mice (versus non-dependent female mice) but equivalent efficacy across male mice and both groups of male and female rats.
We also examined the ability of agmatine to treat thermal and mechanical hyperalgesia symptoms exhibited by alcohol-dependent male and female rats. In the current set of studies, we examined the ability of agmatine to reduce escalated ethanol drinking in complementary models of AUD where adult male and female mice and rats were made dependent via chronic, intermittent ethanol vapor exposure (CIE). Agmatine is an endogenous neuromodulator that has been previously implicated in the regulation of reward and pain processing.
Future effective therapeutics for AUD may need to exhibit the ability to reduce drinking as well as alleviate co-morbid conditions such as pain, as well as take mechanistic sex differences into consideration. Within this framework, alcohol may be used in excessive amounts to alleviate withdrawal-related symptoms, such as hyperalgesia. Alcohol use disorder (AUD) is a chronic, relapsing disorder characterized by an escalation of drinking and the emergence of negative affective states over time.
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