Perinatal exposure to alcohol reduces the expression of complexins I and II.

Perinatal exposure to alcohol (PEA) induces general developmental and specific neuropsychiatric disturbances. Ethanol affects amino acid neurotransmission and synaptic plasticity. We were interested in the transcriptional effects of ethanol on the expression of complexins I and II, two synaptic vesicle proteins (SVP) with relevance for cognition and memory. We exposed pregnant Wistar inbred rats (N=4) and their pups until postnatal day 8 (P8) in vapor chambers and performed in situ-hybridizations regarding complexins I and II at P8 as well as neurobehavioral testing in adult animals of the same litters. At P8, serum ethanol levels of 281+/-58 mg/dl were achieved. PEA animals presented a pronounced retardation of postnatal growth. Significantly lower expression levels of complexin I was observed in CA1, together with trends of reductions in other hippocampal and cortical regions. Complexin II was found reduced in anterior cingulate, prefrontal and fronto-parietal cortex. Adult rats of exposed litters showed worse performance in hippocampus-dependent learning (Morris water maze). The observed suppression of complexins I and II reveals disturbed synaptic plasticity and corresponds with long lasting, ethanol-induced deficits of learning and memory. Further investigations should focus on other synaptic vesicle protein genes in order to unravel the molecular basis of ethanol-induced neurocognitive disabilities.

Cocaine-induced dopamine overflow within the nucleus accumbens measured by in vivo microdialysis: a meta-analysis.

A meta-analysis was conducted on data obtained from published articles which used in vivo microdialysis to assess dose-response curves of cocaine on dopamine (DA) overflow within the nucleus accumbens (NAC). Different experimental and biological parameters such as route of administration (ip, sc, iv, local), rat and mouse strains, gender, age aspects, and regions cannulated (NAC core and shell) were considered. Data from 116 experiments involving 833 animals (out of 266 publications) fulfilled our selection criteria and were analyzed in relation to absolute basal DA levels, the maximum peak of DA overflow (peak [%] baseline) and the time when this peak (peak time) occurred. Our meta-analysis revealed that absolute basal DA levels lie at 2.39 nM (median of all experiments) and that cocaine-induced DA overflow in the NAC is significantly enhanced in a linear dose-response fashion within the applied dose range as the regression function increases following either iv or ip administration. Peak time was reached fastest in iv experiments and slowest following local application. Furthermore, it was shown in ip experiments that the higher the dose, the longer it took to reach the zenith. Results from the NAC shell region displayed greater DA overflow as compared with the NAC core. DA overflow properties following cocaine treatment in mice did not differ from that in rats. Thus, neither species differences nor other biological factors such as, age, gender, and rat/mouse strain have a pronounced impact on cocaine-induced DA overflow. Technical parameters of the microdialysis procedure such as calcium concentration of the perfusion medium and collected sample amount have also no significant effect in terms of DA overflow properties (peak [%] baseline and peak time) following cocaine treatment. In conclusion, these data may be deemed useful for textbook knowledge and a better comparability of data given by the generalization of already existing data as well as for investigators in maximizing the effect of cocaine-induced DA overflow. Finally, this study examplifies how meta- analyses may be applied to a wide range of data within the field of neurochemistry.

Increase of spiny I activity in striatum after development of context-dependent sensitization of catalepsy in rats.

In this study, it was investigated whether context-dependent sensitization of catalepsy changes the firing pattern in striatum. Rats were treated with either haloperidol (0.5 mg/kg i.p.) or saline, and tested on catalepsy with a concomitant single-unit measurement of the spiny I activity. Administration of haloperidol caused sensitization of catalepsy as measured on bar and grid. Concurrent within this behavioral change, spike-frequency increased over the course of the testing days in haloperidol-treated rats whereas the spike-frequency remained unchanged in saline-treated animals. Burst-frequency remained unchanged within both treatment groups over the days. In conclusion, sensitization of catalepsy is represented by striatal cellular activity as indicated by increases in spike-frequency of spiny I neurons.

Burst activity of spiny projection neurons in the striatum encodes superimposed muscle tetani in cataleptic rats.

Catalepsy of animals represents a condition of akinesia and high rigidity of muscles. Catalepsy is a model for Parkinson's disease. The activity of spiny projection neurons in the striatum is correlated with different groups of muscles in rats or primates. Burst activity is a typical characteristic of spiny projection neurons in the state of Parkinson's disease. Rats were treated with 0.5 mg/kg haloperidol to induce a cataleptic state for 180 s. Spiny projection neuronal activity in striatum was measured to detect changes in spike frequency. Triggers were set manually when the rats increased their muscle tone superimposed on the already existing tetanus of the forelimb muscles. The results showed a clear correlation of the occurring triggers and the burst activity in the striatum. During such a burst event, rats did not move but showed this typical superimposed muscle tetanus. A possible explanation is that the intention to move is encoded in the burst activity of spiny projection neurons in the striatum while the execution of the movement is blocked. But also bursts that are not correlated with the short-term superimposed muscle tetanus occurred.