Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The relationship between amphetamine-induced stereotyped behavior and a neuroendocrine index of arousal, plasma corticosterone (CCS), was investigated. 6-Hydroxydopamine lesions of the caudate-putamen, which produced dopamine depletions of 60%, blocked stereotypy and prolonged the elevation in corticosterone associated with d-amphetamine treatment (5 mg/kg). Similar dopamine depleting lesions of the nucleus accumbens, which attenuated the locomotor, but not the stereotypic, response to AMPH did not have this effect on CCS. This pattern of results supports the hypothesis that stereotypy has a coping function which may serve to alter arousal and further suggests important differences between the nigrostriatal and mesolimbic dopamine projections in modulating the responsiveness of the neuroendocrine system. These results have implications for understanding the function of behavioral stereotypies common to a number of psychopathological conditions, including schizophrenia and childhood autism.
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PMID:Attenuation of amphetamine-stereotypy by mesostriatal dopamine depletion enhances plasma corticosterone: implications for stereotypy as a coping response. 270 84

Latent inhibition describes a process by which pre-exposure of a stimulus without consequence retards the learning of subsequent conditioned associations with that stimulus. It is well established that latent inhibition in rats is impaired by increased dopamine function and potentiated by reduced dopamine function. Previous evidence has suggested that these effects are modulated via the meso-accumbens dopamine projections. We have now undertaken three experiments to examine this issue directly, especially in the light of one study in which latent inhibition was reported to be unaffected by direct injection of amphetamine into the accumbens. Latent inhibition was studied using the effect of pre-exposure of a tone stimulus on the subsequent formation of a conditioned emotional response to the tone. 6-Hydroxydopamine-induced lesions of dopamine terminals in the nucleus accumbens resulted in potentiation of latent inhibition. Bilateral local injections of the dopamine antagonist haloperidol into the nucleus accumbens (0.5 microg/side) before conditioning also potentiated latent inhibition. Moreover, such injections were able to reverse the disruptive effect of systemic amphetamine (1mg/kg, i.p.) on latent inhibition. Bilateral local injection of amphetamine (5 microg/side) into the nucleus accumbens before conditioning was able to disrupt latent inhibition, provided that it was preceded by a systemic injection of amphetamine (1mg/kg) 24h earlier.We conclude that the attenuation of latent inhibition by increased dopamine function in the nucleus accumbens is brought about by impulse-dependent release of the neurotransmitter occurring at the time of conditioning. The previously reported failure to disrupt latent inhibition with intra-accumbens amphetamine is probably due to impulse-independent release of dopamine. The implications of these conclusions for theories linking disrupted latent inhibition to the attentional deficits in schizophrenia, and to the dopamine theory of this disorder, are discussed.
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PMID:Modulation of latent inhibition in the rat by altered dopamine transmission in the nucleus accumbens at the time of conditioning. 1111 41

Rearing rats in social isolation from weaning into adulthood leads to deficits in prepulse inhibition and alterations in monoamine systems that modulate prepulse inhibition. For example, rats reared in social isolation have elevated dopamine levels in the nucleus accumbens. Previous studies in rats have shown that nucleus accumbens dopamine depletion with 6-hydroxydopamine blocks the prepulse inhibition-disruptive effects of amphetamine, an indirect dopamine agonist. We tested the hypothesis that prepulse-inhibition deficits in isolation-reared rats are dependent on elevated dopamine levels in the nucleus accumbens. Specifically, we examined whether nucleus accumbens dopamine depletion would attenuate the isolation-induced disruption of prepulse inhibition. Isolation-housed female Long-Evans rats exhibited deficient prepulse inhibition. At 9 weeks post weaning, bilateral injections of 6-hydroxydopamine (8 microg/side) or ascorbic acid vehicle (0.1%) into the nucleus accumbens of social and isolation-reared rats were performed (8-10 rats per group). One week after surgery, prepulse inhibition deficits were exhibited by isolation-reared rats that received vehicle infusion into the nucleus accumbens, but not by those that received 6-hydroxydopamine infusions into the nucleus accumbens. 6-Hydroxydopamine infusions did not significantly change prepulse inhibition in socially reared rats. Behavioral and neurochemical evidence of nucleus accumbens dopamine depletion included: 1) a blockade of amphetamine-stimulated locomotor activity in nucleus accumbens 6-hydroxydopamine-infused isolated and socially reared rats; and 2) high performance liquid chromatography measurements demonstrating a significant depletion of accumbens dopamine and its major metabolites, in addition to decreases in dopamine, homovanillic acid, and 3,4-dihydroxyphenylacetic acid levels in the frontal cortex and anterior caudate. These data indicate that dopamine in the nucleus accumbens plays an essential role in the prepulse inhibition deficits associated with isolation rearing in female Long-Evans rats. The implication of a central role of nucleus accumbens dopamine in prepulse inhibition deficits in an animal model provides further evidence for a link between overactive dopamine function and sensorimotor-gating deficits in patients with schizophrenia.
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PMID:Dopamine depletion of the nucleus accumbens reverses isolation-induced deficits in prepulse inhibition in rats. 1276 84