Serotonergic involvement in methamphetamine-induced locomotor activity: a detailed pharmacological study.

The mechanism by which the psychostimulant methamphetamine (METH) increases locomotor activity may be attributable to indirect activation of serotonin (5-HT) and dopamine (DA) receptors. In the present study, the ability of the serotonin reuptake inhibitor fluvoxamine, 5-HT(1A), 5-HT(1B), 5-HT(2A) and 5-HT(2C) receptor antagonists WAY100635, GR127935, M100907 and SB242084, and the 5-HT(2C) receptor agonists WAY163909 and Ro 60-0175 or the 5-HT synthesis inhibitor para-chlorophenylalanine (pCPA) to alter METH-induced hyperactivity was analysed. Further, for comparative purposes, the involvement of the DA D(1) and D(2) receptor antagonists SCH23390 and haloperidol, D(2) partial agonists terguride, (-)3PPP and aripiprazole and finally clozapine were assessed.

The mGluR2/3 agonist LY379268 reverses post-weaning social isolation-induced recognition memory deficits in the rat.

Rationale: Current antipsychotics are ineffective at treating the negative and cognitive symptoms of schizophrenia, so there is a substantial need to develop more effective therapeutics for this debilitating disorder. The type II metabotropic glutamate receptor (mGluR2/3) is a novel, potential therapeutic target requiring evaluation in appropriate preclinical models of schizophrenia.

Objective: This study evaluated the potent, selective mGluR2/3 agonist, LY379268, on the behavioural deficits induced by rearing rat pups in social isolation from weaning, a neurodevelopmental model of schizophrenia, to investigate its antipsychotic potential.

Antipsychotic medication: the potential role of 5-HT(1A) receptor agonism.

Schizophrenia is a complex psychiatric disorder characterised by positive and negative symptoms, cognitive impairments, attentional problems, anxiety and depressive symptoms. The use of atypical antipsychotics has generally improved clinical outcome yet medical need remains in the treatment of this disease. The potential use of 5-HT(1A) receptor agonism is emerging as one potential area that could be exploited to improve clinical management of the disease.

Serotonergic approaches in the development of novel antipsychotics.

Schizophrenia is a chronic, debilitating neuropsychological disease characterised by positive, negative, and cognitive deficits. In recent years, new pharmacological treatment strategies have been developed to treat the sequalae of schizophrenia based upon more selective receptor activity profiles in the hope that treatment efficacy can be increased without inducing the side-effect profiles seen with current available therapies. One such strategy involves the development of combined (partial) 5-HT(1A) agonists and D(2) receptor (partial) antagonists such as bifeprunox, SLV313, F15063 and SSR-181507 in an attempt to increase therapeutic efficacy of all symptom domains whilst alleviating adverse side effects.