Exposure to Nicotine Produces an Increase in Dopamine D2^High Receptors: A Possible Mechanism for Dopamine Hypersensitivity

ABSTRACT

Dopamine D2 receptors exist in both low- and high-affinity states (D2^High), the latter being the functionally relevant state. Cocaine self-administration produces an increase in D2^High, a phenomenon that could explain why cocaine administration results in hypersensitivity to dopamine, even though drug addicts were found to have a decreased number of striatal dopamine D2 receptors. As nicotine acts through the same mesocortical dopaminergic signaling pathways as other stimulant drugs, which are known to increase the levels of D2^High, we hypothesized that nicotine exposure could produce an increase in D2^High levels. We determined D2^High levels in rats after nicotine administration (1.5 mg/kg/day; 14 days), in rats voluntarily self-administering nicotine using an intravenous self-administration (IVSA) protocol (mean dose 0.5 mg/kg/day; 14 days), as well as after a prolonged withdrawal. An increase in the levels of D2^High was found in rats who had nicotine administered at a uniform dose, as well as in rats who self-administered nicotine via IVSA, but these changes appear to normalize over time, as indicated by lower D2^High levels in rats after a prolonged withdrawal period. We suggest that nicotine-induced elevation in D2^High levels could be participating in hypersensitivity to dopamine following nicotine exposure.

KEYWORDS: :

• Basal ganglia
• cigarette
• D2^High
• dopamine
• incentive
• nicotine
• sensitization
• smoking
• tobacco