Activation of midline thalamic nuclei by antipsychotic drugs

Abstract

The thalamus has been proposed as a site which may be involved in the production of the syndrome of schizophrenia and the response of schizophrenic symptoms to treatment. These studies test whether, consistent with this hypothesis, the activation of thalamic nuclei is a shared property of neuroleptic antipsychotic drugs. Rats were given single doses of the typical high and low potency neuroleptics haloperidol (1 mg/kg) and chlorpromazine (20 mg/kg), the atypical neuroleptics thiroridazine (20 mg/kg) and clozapine (20 mg/kg), the specific dopamine antagonist raclopride (3 mg/kg), the mixed dopamine/serotonin antagonist risperidone (3 mg/kg) or drug-free vehicle. Increased expression of Fos-like protein was utilized as a marker of cellular activation. All drugs tested, including typical and atypical antipsychotic agents, led to similar effects on the midline thalamic paraventricular, centromedian and rhomboid nuclei and the nucleus reuniens. These results suggest that midline thalamic nuclei may participate in neural circuits mediating some of the shared effects of antipsychotic drugs.

Distribution of Dopamine D2-Like Receptors in the Human Thalamus: Autoradiographic and PET Studies

“…These anatomical data suggest that signaling through DA receptors on midline thalamic neurons may convey information to mesocorticolimbic DA terminal fields, particularly the frontal cortices, and thus potentially be involved in the attention deficits seen in schizophrenia ( Kornetsky and Orzack, 1978;Matthysse, 1978). Consistent with this speculation is the fact that neurons of the PVT and other midline/intralaminar nuclei are targets of atypical antipsychotic drugs (Cohen et al, 1998;Deutch et al, 1995). In addition, several recent studies have reported decreased numbers of neurons in the mediodorsal nucleus (Pakkenberg, 1990;Popken et al, 2000, Young et al, 2000.…”

Different Effects of Typical and Atypical Antipsychotics on Grey Matter in First Episode Psychosis: the ÆSOP Study

“…The thalamus is part of brain circuits that modulate perception, emotion, and thinking (Crosson and Hughes, 1987), and its volume seems to be reduced in patients with schizophrenia (Andreasen et al, 1994). Owing to its role in integrating brain functions, the thalamus could be involved in mediating the clinical effects of antipsychotic drugs, and it has been indicated as one of the sites of action of both typical and atypical antipsychotic drugs (Cohen et al, 1998(Cohen et al, , 2003. Again, the fact that the thalamus volumes were not different between typicals and atypicals groups would support that both classes of drugs may affect this region, but to a different extent.…”

Alterations of Thalamic Activity in Schizophrenia and in Response to Antipsychotic Drugs Studies in the Legacy of Seymour S. Kety

“…These studies observed antipsychotic drug-induced changes in activity of neurons in the midline thalamic nuclei, including the paraventricular nucleus, the centromedial nucleus, the rhomboid nucleus and the nucleus reuniens (Deutch et al 1995;Cohen and Wan 1996; and see Figure 2). This effect of neuroleptic antipsychotic drugs was observed across a wide range of agents, including the pure dopamine D2 antagonist, raclopride; the typical neuroleptic, haloperidol; the mixed monoamine antagonists, chlorpromazine and thioridazine; the dopamine D2 and serotonin SHT2 antagonists risperidone and olanzapine; and the atypical antipsychotic, clozapine (Cohen et al 1998;Cohen et al unpublished observations).…”

“…Moreover, antipsychotic drugs, which ameliorate the symptoms of schizophrenia, have also been shown to produce changes of activity in the thalamus, as documented both in animals and human subjects (see Cohen et al 1998 for review). These findings are exciting because they identify regions of focal pathology in schizophrenia, as well as provide insight into potential treatment strategies.…”