Repeated administrations of lithium salts (Li2CO3 or LiCl, 60 and 85 mg/kg, respectively, twice a day for five days) to rats increased brain 5-hydroxyindoleacetic acid (5-HIAA) by about 80% and brain serotonin by 15 to 20%. The changes were not due to an inhibition of 5-HIAA transport from brain, but to an increase in the rate of synthesis of brain serotonin. Rate of serotonin synthesis was measured by multiplying the rate constant of 5-HIAA decline, after inhibition of monoamine oxidase, by the steady-state level of 5-HIAA. The calculation indicated that lithium increased the synthesis rate of brain serotonin by about 80%. Moreover, chronic treatment with lithium salts also increased the levels of brain tryptophan by about 70%, suggesting that this could be the mechanism by which lithium stimulates serotonin synthesis.
We studied 90 opioid-dependent subjects, 38 with one or more additional Axis I diagnosis and 52 with no psychiatric comorbidity. There were significant differences between these two groups regarding the methadone dose required for clinical stabilization, but not in the rate of retention in treatment. Dual Diagnosis patients, those with psychiatric comorbidity, required an average stabilization dose of 154 +/- 84 of methadone compared to 99 +/- 49 mg/day for patients whose only Axis I diagnosis was Opioid Dependence. In the 990-day period considered there were no differences between the two groups of patients in terms of retention in treatment.
<i>Objective:</i> The aim of this study was to compare the long-term outcomes of treatment-resistant heroin addicts with and without DSM-IV axis I psychiatric comorbidity (dual diagnosis). <i>Method:</i> 129 heroin addicts who also met criteria for treatment resistance, 66 with one or more DSM-IV axis I psychiatric diagnosis (DD patients), and 63 without DSM-IV axis I psychiatric comorbidity (NDD patients) were monitored prospectively (6 years on average, min. 1, max. 9) along a methadone maintenance treatment program (MMTP). <i>Results:</i> The rates for survival-in-treatment were about 50% for NDD patients and about 70% for DD patients. After 4 years of treatment onwards, such rates tended to become stable. DD patients showed better outcome measures than NDD patients. A significantly higher methadone dose was needed to have DD patients stabilized. <i>Conclusions:</i> Contrary to expectations, treatment-resistant patients with psychiatric comorbidity showed a better long-term outcome than treatment-resistant patients without psychiatric comorbidity.
In non-food-deprived rats a palatable meal induces a transient increase in dopamine output in the prefrontal cortex and nucleus accumbens shell and core; habituation to this response develops with a second palatable meal, selectively in the shell, unless animals are food-deprived. A palatable meal also induces time-dependent modifications in the dopamine and cAMP-regulated phosphoprotein of Mr 32 000 (DARPP-32) phosphorylation pattern that are prevented when SCH 23390, a selective dopamine D(1) receptor antagonist, is administered shortly after the meal. This study investigated whether dopaminergic habituation in the shell had a counterpart in DARPP-32 phosphorylation changes. In non-food-deprived rats, two consecutive palatable meals were followed by similar sequences of modifications in DARPP-32 phosphorylation levels in the prefrontal cortex and nucleus accumbens core, while changes after the second meal were blunted in the shell. In food-deprived rats two consecutive meals also induced similar phosphorylation changes in the shell. Finally, SCH 23390 administered shortly after the first palatable meal in non-food-deprived rats inhibited DARPP-32 phosphorylation changes in response to the first meal, and prevented the habituation to a second meal in terms of dopaminergic response and DARPP-32 phosphorylation changes. Thus, dopamine D(1) receptor stimulation plays a role in the development of habituation.
