| Summary: | Our lab has shown that neonatal treatment with quinpirole, a dopamine D2/D3 agonist, to rats resulted in an increase in dopamine D2-like receptor sensitivity that persists throughout the animal’s lifetime without a change in receptor number, consistent with schizophrenia. Approximately 80-85% of schizophrenics smoke cigarettes, and there is no delineated mechanism for this observation. Our lab has also shown more robust sensitization and accumbal dopamine release in response to nicotine in adolescent rats neontally treated with quinpirole compared to controls. This study analyzed whether environmental enrichment, known to reduce sensitization to psychostimulants, may also reduce or block enhanced sensitization to nicotine in this model. Male and female rats were treated with either quinpirole (1 mg/kg) or saline from postnatal day (P)1-21. After weaning at P21, animals were raised in either environmentally enriched or isolated housing throughout the experiment. Beginning on P33, animals were ip administered either nicotine (0.5 mg/kg free base) or saline 10 min before placement in a square locomotor arena and behavioral activity measured every second day from P33-49. Results revealed that animals given neonatal quinpirole treatment and reared in an enriched environment demonstrated more robust sensitization to nicotine than all other groups. Animals given neonatal quinpirole or saline treatment followed by nicotine in adolescence and raised in isolated housing conditions were equivalent, but demonstrated more robust sensitization compared to enriched rats neonatally treated with saline and administered nicotine in adolescence. Results here show that environmental enrichment enhanced nicotine sensitization in rats neonatally treated with quinpirole, which is in contrast to the blockade of sensitization to nicotine which has previously been shown in normal animals. Importantly, these results show that increases in D2 receptor sensitivity interacts with environmental enrichment differently than in normal animals and the manner in which the animal responds to nicotine, which may have implications towards smoking cessation in schizophrenia.
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