Male rats treated with subchronic PCP show intact olfaction and enhanced interest for a social odour in the olfactory habituation/dishabituation test.

The olfactory system participates in many sensory processes, and olfactory endophenotypes appear in a variety of neurological disorders such as Alzheimer's and Parkinson's disease, depression and schizophrenia. Social withdrawal is a core negative symptom of schizophrenia and animal models have proven to be invaluable for studying the neurobiological mechanisms and cognitive processes behind the formation of social relationships. The subchronic phencyclidine (PCP) rat model is a validated model for negative symptoms of schizophrenia, such as impaired sociability. However, the complete range of social behaviour and deficits in the model are still not fully understood. Intact rodent olfaction is essential for a wide range of social behaviour and disrupted olfactory function could have severe effects on social communication and recognition. In order to examine the olfactory ability of male rats treated with subchronic PCP, we conducted an olfactory habituation/dishabituation test including both non-social and social odours. The subchronic PCP-treated rats successfully recognized and discriminated among the odours, indicative of intact olfaction. Interestingly, the subchronic PCP-treated rats showed greater interest for a novel social odour compared to the saline-treated rats and the rationale remains to be elucidated. Our data indicate that subchronic PCP treatment does not disrupt olfactory function in male rats. By ruling out impaired olfaction as cause for the poor social interaction performance in subchronic PCP-treated rats, our data supports the use of NMDA receptor antagonists to model the negative symptoms of schizophrenia.

Effects of 2-bromoterguride, a dopamine D2 receptor partial agonist, on cognitive dysfunction and social aversion in rats.

RATIONALE: 2-Bromoterguride, a dopamine D2 receptor partial agonist with antagonist properties at serotonin 5-HT2A receptors and α2C-adrenoceptors, meets the prerequisites of a putative atypical antipsychotic drug (APD). We recently showed that 2-bromoterguride is effective in tests of positive symptoms of schizophrenia in rats without inducing extrapyramidal side effects or metabolic changes. OBJECTIVE: In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating. In addition, we used subchronic PCP treatment to produce cognitive deficits and social aversion, and assessed the effect of 2-bromoterguride on the performance in the novel object recognition (NOR) task (model for studying cognitive deficit symptoms of schizophrenia) and the social interaction test (model for studying negative symptoms of schizophrenia). Finally, we extended the side effect profile of 2-bromoterguride by measuring the prolactin response to systemic administration of the drug in rats. RESULTS: Treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) reversed PPI deficits induced by apomorphine and PCP, respectively. Subchronic PCP induced impairments in object memory and social interaction behavior which were ameliorated by 2-bromoterguride but not by clozapine and aripiprazole, respectively. Prolactin concentration in blood serum was not elevated at 1, 2, or 4 h post-2-bromoterguride treatment, which further supports the safe and effective use of this drug. CONCLUSIONS: Our data support 2-bromoterguride as a promising APD candidate due to its beneficial effect on cognitive impairments and negative symptoms of schizophrenia.

2-Bromoterguride-a potential atypical antipsychotic drug without metabolic effects in rats.

RATIONALE: Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. OBJECTIVE: To extend our knowledge on the antipsychotic effects of 2-bromoterguride, we used convergent preclinical animal models and tests; i.e., conditioned avoidance response (CAR), predictive of antipsychotic-like effects; Fos protein expression, a molecular marker for (atypical) antipsychotic activity; wet dog shake behavior, a test for the in vivo effects of drugs acting on central 5-HT2A receptors; and investigated metabolic changes as a common side effect of atypical antipsychotic drugs (APDs). RESULTS: Acute treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) decreased the CAR at 30, 90, and 270 min post-injection in rats without inducing escape failures at any time. Fos protein expression, as shown by Western blotting, was enhanced by 2-bromoterguride in the nucleus accumbens (NAc), the dorsolateral striatum (dStr), and the medial prefrontal cortex (mPFC). (±)-2,5-Dimethoxy-4-iodoamphetamine (DOI)-induced wet dog shakes in rats were reduced by 2-bromoterguride. Chronic treatment with 2-bromoterguride did not affect metabolic parameters such as body weight development and body fat composition as well as behavioral parameters such as food intake and locomotor activity. CONCLUSIONS: Our data suggest that 2-bromoterguride is a promising candidate in the treatment of schizophrenia due to its atypical antipsychotic-like activity and its inability to induce weight gain.

The Value of Molecular vs. Morphometric and Acoustic Information for Species Identification Using Sympatric Molossid Bats.

A fundamental condition for any work with free-ranging animals is correct species identification. However, in case of bats, information on local species assemblies is frequently limited especially in regions with high biodiversity such as the Neotropics. The bat genus Molossus is a typical example of this, with morphologically similar species often occurring in sympatry. We used a multi-method approach based on molecular, morphometric and acoustic information collected from 962 individuals of Molossus bondae, M. coibensis, and M. molossus captured in Panama. We distinguished M. bondae based on size and pelage coloration. We identified two robust species clusters composed of M. molossus and M. coibensis based on 18 microsatellite markers but also on a more stringently determined set of four markers. Phylogenetic reconstructions using the mitochondrial gene co1 (DNA barcode) were used to diagnose these microsatellite clusters as M. molossus and M. coibensis. To differentiate species, morphological information was only reliable when forearm length and body mass were combined in a linear discriminant function (95.9% correctly identified individuals). When looking in more detail at M. molossus and M. coibensis, only four out of 13 wing parameters were informative for species differentiation, with M. coibensis showing lower values for hand wing area and hand wing length and higher values for wing loading. Acoustic recordings after release required categorization of calls into types, yielding only two informative subsets: approach calls and two-toned search calls. Our data emphasizes the importance of combining morphological traits and independent genetic data to inform the best choice and combination of discriminatory information used in the field. Because parameters can vary geographically, the multi-method approach may need to be adjusted to local species assemblies and populations to be entirely informative.