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 as 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 1-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, D 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
B
Department of Psychology, East Tennessee State University, Johnson City, TN 37614, USA.
Lehmann
Julia
J
Cope
Zackary A
ZA
Brown
Russell W
RW
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D006948:Hyperkinesis; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage*; D011759:Pyrrolidines / Q000494:pharmacology; D019257:Quinpirole / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D050637:Receptors, Dopamine D3 / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D012727:Sex Characteristics
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D009281:Naphthalenes; D011759:Pyrrolidines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D012457:Salicylamides; D019257:Quinpirole; D009538:Nicotine; C045989:eticlopride; C097285:nafadotride