Sex Differences in Nicotine Sensitization and Conditioned Hyperactivity in Adolescent Rats Neonatally Treated with Quinpirole: Role of D2 and D3 Receptor Subtypes
Neonatal quinpirole treatment in rats produces increased sensitivity of dopamine D2-like receptors throughout the animal's lifetime, referred to D2 priming. There is little information on the effects of nicotine in adolescent rats, especially in a model that has clinical relevance to psychosis where increased D2 receptor sensitivity is common. Male and female rats were treated with quinpirole (1 mg/kg) or saline from postnatal (P) day P21, given nicotine (0.5 mg/kg) or saline from P33 through P49, and placed into a locomotor arena for behavioral testing. Nicotine or saline treatment was preceded by the D2-like receptor antagonist eticlopride, D3 antagonist nafadotride, or saline. Conditioned hyperactivity was analyzed on P50 in the same context in a drug-free test. In females, D2 priming increased the locomotor response to acute nicotine, but did not affect subsequent nicotine sensitization, and only non–D2-primed females demonstrated conditioned hyperactivity. Eticlopride and nafadotride blocked behavioral sensitization, although nafadotride was more effective at blocking nicotine-conditioned hyperactivity in females. In males, D₂ priming enhanced sensitization to nicotine and produced conditioned hyperactivity, which were blocked by eticlopride and nafadotride. These results have implications for psychosis and comorbidity of nicotine abuse in adolescence.
Sheppard, Brianna; Lehmann, Julia; Cope, Zackary A.; and Brown, Russell W.. 2009. Sex Differences in Nicotine Sensitization and Conditioned Hyperactivity in Adolescent Rats Neonatally Treated with Quinpirole: Role of D2 and D3 Receptor Subtypes. Behavioral Neuroscience. Vol.123(6). 1296-1308. https://doi.org/10.1037/a0017536 ISSN: 1939-0084