Differential role of serotonergic projections arising from the dorsal and median raphe nuclei in locomotor hyperactivity and prepulse inhibition.

While an involvement of brain serotonin systems in schizophrenia has been suggested by many studies, the relative role of different serotonergic projections in the brain remains unclear. We therefore examined the effects of selective brain serotonin depletion on psychotropic drug-induced locomotor hyperactivity and prepulse inhibition, two animal models of aspects of schizophrenia. Pentobarbital-anesthetized (60 mg/kg, i.p.) male Sprague-Dawley rats were stereotaxically microinjected with 1 microl of a 5 microg/microl solution of the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT) into either the dorsal or median raphe nucleus. At 2 weeks after the surgery, rats with dorsal raphe lesions did not show changes in psychotropic drug-induced locomotor hyperactivity, but displayed partial disruption of prepulse inhibition. In contrast, rats with median raphe lesions showed significant enhancement of phencyclidine-induced, but not amphetamine-induced locomotor hyperactivity and a marked disruption of prepulse inhibition. These results provide evidence for differential involvement of serotonergic projections in locomotor hyperactivity and prepulse inhibition. This study may help to explain the role of different serotonin projections in the brain in the pathophysiology of schizophrenia.

Production of generalized learning deficit and permanent growth stunting by bilateral brain stem lesions.

Bilateral lesions of the globus pallidus, ventrolateral thalamus, substantia nigra, or the median raphe produce a generalized learning deficit in rats. Bilateral lesions of the dorsomedial hypothalamic nuclei stunt growth in rats without significantly disturbing endocrine functions and without producing a generalized learning deficit. Globus pallidus, ventrolateral thalamus, substantia nigra, median raphe, and dorsomedial hypothalamic nuclei lesions were produced in weanling Sprague-Dawley rats to compare their effect on physical growth. At approximately 72 d of age, all lesions had resulted in reduced body wt, tail length, and tibial length. The differences lacked significance only in body wt after median raphe lesions and tail length after ventrolateral thalamus lesions. In rats with the generalized learning deficit, body size was most stunted after substantia nigra lesions. Tibial epiphyseal width was modestly increased in rats with the generalized learning deficit. Food intake/average body wt ratio in substantia nigra and dorsomedial hypothalamic nuclei rats did not differ significantly from control values. Decreases in brain, heart, liver, kidney, and testes tended to occur after all the lesions, but brain and testis organ wt/body wt ratios were either increased or unchanged. We conclude that brain lesions producing a generalized learning deficit in rats result in impaired physical growth. The results indicated that the stunted animals maintain adequate food intake and have normal growth hormone function. The anatomical substrate for generalized learning impairment may overlap with that of a set point for body size.