Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and 'schizophrenia-related' behaviors.

There is growing evidence implicating dysfunctional glutamatergic neurotransmission and abnormal interactions between the glutamate and dopamine (DA) systems in the pathophysiology of various neuropsychiatric disorders including schizophrenia. The present study evaluated knockout (KO) mice lacking the L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) GluR1 receptor subunit for a range of behaviors considered relevant to certain symptoms of schizophrenia. KO showed locomotor hyperactivity during exposure to open field and in response to a novel object, but normal activity in a familiar home cage. Open field locomotor hyperactivity in KO was effectively normalized to WT levels by treatment with the DA antagonist and neuroleptic haloperidol, while locomotor stimulant effects of the NMDA receptor antagonist MK-801 were absent in KO. Social behaviors during a dyadic conspecific encounter were disorganized in KO. KO showed deficits in prepulse inhibition of the acoustic startle response. In vivo chronoamperometric measurement of extracellular DA clearance in striatum demonstrated retarded clearance in KO. These data demonstrate behavioral abnormalities potentially pertinent to schizophrenia in GluR1 KO, together with evidence of dysregulated DA function. Present findings provide novel insight into the potential role of GluR1, AMPA receptors and glutamate x DA interactions in the pathophysiology of schizophrenia and other neuropsychiatric conditions.

Galanin as a modulator of anxiety and depression and a therapeutic target for affective disease.

Galanin is a 29 amino-acid (30 in humans) neuropeptide with a close functional relationship with neurotransmitter systems implicated in the pathophysiology and treatment of depression and anxiety disorders. In rodent models of depression-related behavior, treatment with galanin or compounds with agonist actions at galanin receptors has been shown to affect depression-related behaviors and the behavioral and neurochemical effects of antidepressants. Treatment with clinically efficacious antidepressants alters galanin and galanin receptor gene expression in rodents. Rodent anxiety-like behaviors appear to be modulated by galanin in a complex manner, with studies showing either increases, decreases and no effects of galanin treatments and galanin mutations on anxiety-like behavior in various tasks. One concept to emerge from this literature is that galanin recruitment during extreme behavioral and physiological provocations such as stress and opiate withdrawal may serve to attenuate negative emotional states caused by noradrenergic hyperactivation. The specific galanin receptor subtypes mediating the anxiety- and depression-related effects of galanin remains to be determined, with evidence supporting a possible contribution of GalR1, GalR2 and GalR3. While our understanding of the role of galanin as a modulator of emotion remains at an early stage, recent progress in this rapidly evolving field raise possibility of that galanin may represent a target for the development of novel antidepressant and anxiolytic drug treatments.

Phytosterols in sea buckthorn (Hippophaë rhamnoides L.) berries: identification and effects of different origins and harvesting times.

Sterols in seeds, pulp/peel fractions, and whole berries of sea buckthorn (Hippophaë rhamnoides L.) samples belonging to two major subspecies (sinensis and rhamnoides) from Finland and China were analyzed as TMS derivatives by gas chromatography-mass spectrometry after saponification of the oils. The total sterol contents in the seeds, the fresh pulp/peel, and the whole berries were 1200-1800, 240-400, and 340-520 mg/kg, respectively. The corresponding values in the extracted oils were 12-23, 10-29, and 13-33 g/kg. Sitosterol constituted 57-76 and 61-83%, respectively, of the seed and pulp/peel sterols. The sterol content and composition showed little variation between subspecies and collection sites. Different harvesting dates showed significant effects on the levels of some sterols both in the seeds and in the pulp/peel. The sterol profiles obtained are useful for characterizing sea buckthorn and detecting adulterations of the valuable oils. The information provided by the present investigation is also important for further chemical investigation of sea buckthorn sterols and industrial utilization of the berries as a raw material of functional foods.