This research study examined the effects of high levels of sugar intake on mental health in marijuana smokers. Because the literature demonstrates a similarity between refined sugar and other commonly addictive drugs, those who ingest a higher percentage of dietary sugar will score more poorly on the DASS21, meaning that with higher levels of sugar ingestion, a greater deficit in mental health functioning will be measurable. Of 16 participants, nine were female and seven were male, and the participants ranged from a normal weight to obese. The results did support the hypothesis of sugar dependence. This has implications for future studies on the impact of sugar on mental health. The results to this study may provide insight into potential for greater understanding of eating disorders associated with sugar dependence, thereby potentially leading to the development of more effective treatment options.

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 Page 13 of 35 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.

Aims: Neonatal quinpirole (a dopamine D2-like agonist) treatment to rats has been shown to increase dopamine D2 receptor sensitivity throughout the animal’s lifetime, and increased dopamine D2 sensitivity is a hallmark of schizophrenia. Schizophrenics are 3 to 4 times more likely to smoke than the normal population, but there is no delineating mechanism. Aim 1: Behaviorally test a rewarding versus averisve dose of nicotine in adolescent rats neonatally treated with quinpirole tested in a place preference paradigm; Aim 2: Analyze phosphorylated cylic AMP response element bidning protein (CREB) in brain areas that mediate drug reward. Methods: Rats were neonatally treated with quinpirole from postnatal days (P)1- 21. After two drug free preferene tests were given in a place preference shuttle box at P41-42, animals were conditioned with saline, a 0.6 or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A post-conditioning test was given 24 h after conditioning. Time in the paired and unpaired context were measured. Approximately 24 h after the post-condioning test, brain tissue was harvested, flash frozen, and later analyzed for pCREB in the dorsal and nucleus accumbens. Results: Results revealed that neonatal quinpirole enhanced the rewarding associative effects of the lower dose of nicotine compared to animals neonatally treated with saline and conditioned with the same dose of nicotine, which showed a slight place preference. Interestingly, although neonatal saline animals conditioned with the higher dose of nicotine demonstrated conditioned place aversion, neonatal quinpirole treated animals demonstrated no aversion to this same dose. Analyses for p-CREB will be presented. Conclusions: Rats neonatally treated with quinpirole demonstrate an enhancement of the rewarding properties of nicotine, but do not demonstrate an aversion to higher doses of nicotine. These data are congruent with recent self-administration data in our lab, and suggest that increases of dopamine D2 sensitivity may blunt aversive aspects of nicotine.

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.

Abstract available through American Journal of Epidemiology.

Abstract available through Clinical Pharmacology in Drug Development.

Schizophrenics are significantly more likely to smoke cigarettes than the general population. In Experiment 1, we analyzed the effects of a rewarding versus an aversive dose of nicotine using the neonatal quinpirole (QUIN; dopamine D2/D3 agonist) model of schizophrenia. In Experiment 2, we examined the effects of antipsychotic treatment upon the associative reward of nicotine within this same model. Neonatal QUIN treatment to rats results in increased dopamine D2 receptor sensitivity throughout the rat’s lifetime, consistent with schizophrenia. Rats were neonatally treated with QUIN (1 mg/kg dose) or saline from postnatal days (P)1-21. Animals were then raised to P41 without any further drug treatment. Subjects were administered two consecutive pre-conditioning drug free preference tests in a three chamber shuttle box on P41 and P42 to determine initial preference. In Experiment 1, beginning on P43, animals were conditioned with saline, a 0.6 mg/kg or a 1.8 mg/kg free base dose of nicotine for eight consecutive days. A drug free post-conditioning preference test was given on P51. Approximately 24 h following the post-conditioning test, brain tissue was harvested and analyzed for mammalian target of rapamycin (mTOR) and phosphorylated-CREB (pCREB) in the nucleus accumbens. In Experiment 2, animals were treated identically as in Experiment 1, but were conditioned with nicotine which was preceded by an injection of either a typical antipsychotic (haloperidol, 0.5 mg/kg dose) or an atypical antipsychotic (clozapine, 2.5 mg/kg dose) for a period of eight days which was followed by a drug free preference test. In both experiments, the difference between time spent in the paired context between pre-test and post-test was utilized as a measure of associative reward. Results revealed that neonatal QUIN enhanced the rewarding effects of nicotine, but neutralized the aversive effects compared to controls. Neonatal QUIN also significantly decreased accumbal mTOR and pCREB results will be presented. In Experiment 2, we found that treatment with clozapine reduced the enhancement of nicotine conditioned place preference, but haloperidol completely reduced nicotine place preference to control levels. These findings show that neonatal QUIN enhances the rewarding associative effects of nicotine, and that the typical antipsychotic haloperidol was more effective at eliminating the associative rewarding effects of nicotine likely due to its potent D2 antagonistic effects.

Abstract available through American Journal of Epidemiology.

Abstract available through Clinical Pharmacology in Drug Development.

Many patients suffering from depressive disorders are refractory to treatment with currently available antidepressant medications, while many more exhibit only a partial response. These factors drive research to discover new pharmacological approaches to treat depression. Numerous studies demonstrate evidence of inflammation and elevated oxidative stress in major depression. Recently, major depression has been shown to be associated with elevated levels of DNA oxidation in brain cells, accompanied by increased gene expression of the nuclear base excision repair enzyme, poly(ADP-ribose) polymerase-1. Given these findings and evidence that drugs that inhibit poly(ADP-ribose) polymerase-1 activity have antiinflammatory and neuroprotective properties, the present study was undertaken to examine the potential antidepressant properties of poly(ADP-ribose) polymerase inhibitors.