Erratum: Adjunctive treatment with mianserin enhances effects of raclopride on cortical dopamine output and, in parallel, its antipsychotic-like effect ||Reprinted from Neuropsychiatric Disease and Treatment 2005, 1(3) 253–260||

Charlotte Wiker, Love Linnér, Marie-Louise Wadenberg, Torgny H Svensson

Section for Neuropsychopharmacology, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden

Abstract: Clinical studies indicate that adjunctive treatment with the antidepressant drug mianserin, a 5-hydroxytryptamine (5-HT)_2A/C receptor antagonist and an α₂- and α₁-adrenoceptor antagonist, may enhance the effect of conventional antipsychotic drugs in schizophrenia, in particular on negative symptoms such as withdrawal retardation, akathisia, and some aspects of cognitive impairment. Here, we have examined the effect of mianserin in combination with the selective dopamine (DA) D_2/3 receptor antagonist raclopride on conditioned avoidance response (CAR), a preclinical test of antipsychotic efficacy with high predictive validity; catalepsy, a preclinical test of extrapyramidal side effect liability; and DA output in the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAC), respectively. Mianserin (5 mg/kg intraperitoneal) significantly enhanced the suppressant effect of a low dose of raclopride (0.1 mg/kg subcutaneous) on CAR without any increase in catalepsy. Administration of raclopride to rats pretreated with mianserin resulted in a large enhancement of DA output in the mPFC and, at the same time, a small but significant reduction in the raclopride-induced DA output in the NAC. These experimental results indicate that adjunctive treatment with mianserin to a typical D₂ antagonist generates an atypical antipsychotic profile.

Keywords: adjunctive mianserin, typical antipsychotic drugs, dopamine, prefrontal cortex, atypicality