Research has revealed that schizophrenics are significantly more likely to smoke cigarettes than the general population, and consume nicotine products at a much more prevalent rate. Further exacerbating this issue, it has been previously demonstrated in clinical populations that the type of antipsychotic treatment administered (typical versus atypical) may result in either an increase or a decrease of already heightened smoking behavior within the schizophrenic population. With these clinical issues in mind, the present study sought to examine the effects of antipsychotic treatment upon the associative reward of nicotine within the neonatal quinpirole model of schizophrenia. We found that treatment with the typical antipsychotic haloperidol blocked the associative reward of nicotine. Clozapine, an atypical antipsychotic, merely reduced the rewarding effects. These findings illustrate the centrality of the dopamine system, specifically the D2 receptor subtype, as an underlying mechanism of the rewarding effects of nicotine among rodents neonatally treated with quinpirole.

This study was designed to investigate the effects of acute eticlopride (0.02 mg/kg, D2 antagonist) treatment, given immediately before training, in rats neonatally treated with quinpirole, which has been shown to produce long-term D2 receptor supersensitization. Rats were given quinpirole (1mg/kg) or saline treatment from P1-21. Beginning on P22, rats were administered eticlopride or saline (i.p.) fifteen mins before each of seven days of training. Rats were tested on the Morris water task (MWT). For the first three consecutive days, rats were tested on the place version of the MWT with a stationary platform. Animals were given 24 training trials followed by a probe trial, and swim patterns were analyzed with platform removed. The next day, animals began testing on the match-to-place version for four consecutive days and two daily trials were given with the platform moved to a new location each day. On both the search time and target visit measures of the probe trial, animals neonatally treated with quinpirole demonstrated a deficit, and eticlopride eliminated this deficit. Interestingly, animals neonatally treated with saline but given eticlopride before training also demonstrated a deficit on both measures. On the match-to-place version, the difference in latency to locate the platform between the two daily trials served as the dependent measure. Similar to the MWT place version, eticlopride treatment eliminated deficits produced by neonatal quinpirole treatment on this task, and eticlopride produced a deficit in saline controls. This study demonstrates that in a model of dopamine D2 supersensitivity, it appears that the increased sensitivity of the D2 receptor is important for cognitive function.

This review focuses on nicotine comorbidity in schizophrenia, and the insight into this problem provided by rodent models of schizophrenia. A particular focus is on age differences in the response to

We have shown that repeated neonatal quinpirole (QUIN; a dopamine D2-like receptor agonist) treatment in rats produces long-lasting supersensitization of dopamine D2 receptors that persists into adulthood but without producing a change in receptor number. The current study was designed to analyze the effects of neonatal QUIN on auditory sensorimotor gating as measured through prepulse inhibition (PPI). Male and female Sprague–Dawley rats were neonatally treated with QUIN (1mg/kg) or saline from postnatal days (P)1–21. At P60, the number of yawns was recorded for a 1h period in response to an acute QUIN (1mg/kg) injection as yawning is a D2-like receptor mediated behavioral event. Five days later, rats began (PPI) behavioral testing in two phases. In phase I, three different prepulse intensities (73, 76, and 82dB) were administered 100-ms before a 115dB pulse on 10 consecutive days. In phase II, three different interstimulus intervals (ISI; 50, 100, and 150ms) were inserted between the 73 or 76dB prepulse and 115dB pulse over 10 consecutive days of testing. A PPI probe trial was administered at the end of each phase after an acute 100μg/kgi.p. injection of QUIN to all animals. Replicating previous work, neonatal QUIN enhanced yawning compared to controls, verifying D2 receptor supersensitization. Regarding PPI, neonatal QUIN resulted in deficits across both phases of testing persistent across all testing days. Probe trial results revealed that acute QUIN treatment resulted in more robust PPI deficits in neonatal QUIN animals, although this deficit was related to prepulse intensity and ISI. These findings provide evidence that neonatal QUIN treatment results in deficits of auditory sensorimotor gating in adulthood as measured through PPI.