Altered prepulse inhibition in rats treated prenatally with the antimitotic Ara-C: an animal model for sensorimotor gating deficits in schizophrenia.

RATIONALE: Sensorimotor gating disruption is one of many neurocognitive deficits seen in schizophrenia. Disorganized thought is one of the cardinal symptoms associated with sensorimotor gating. In an attempt to model sensorimotor gating deficits in rats relevant to the neurodevelopmental hypothesis for schizophrenia, we have used prenatal injections of the antimitotic drug, cytosine arabinoside (Ara-C) to subtly perturb the development of the rat CNS and disrupt sensorimotor gating. OBJECTIVE: To produce rats with either basal sensorimotor gating deficits or increased vulnerability to the disruption of sensorimotor function by apomorphine or phencyclidine (PCP). Prepulse inhibition (PPI) of the acoustic startle response was used to assess sensorimotor gating. METHODS: Three different cohorts of pregnant Sprague Dawley female rats were injected with Ara-C (30 mg/kg in saline) or saline at embryonic days 19.5 and 20.5. The Ara-C and control rats were tested for acoustic startle response and PPI at preadolescent and post-adolescent ages; postnatal day (Pnd) 35 and 56, respectively. Apomorphine (2.0 mg/kg) or phencyclidine (3.0 mg/kg), was given prior to PPI sessions in order to disrupt PPI. RESULTS: At Pnd 35, Ara-C treatment did not significantly affect acoustic startle amplitudes or PPI. However, at PND 56, Ara-C treated rats had significantly lower acoustic startle amplitudes and significantly diminished sensorimotor gating. Pharmacological challenge with the dopamine agonist apomorphine and the glutamate antagonist PCP significantly disrupted sensorimotor gating in the control subjects. Apomorphine did not further disrupt the existing deficit in the Ara-C treated rats. Ara-C treatment did not cause gross loss of neuronal tissue, although there was a subtle and variable disorganization of the pyramidal cell layer in the hippocampal CA2/3 region. CONCLUSION: The results provide evidence to suggest that late embryonic exposure to Ara-C disrupts the circuitry involved in mediating PPI. While the dopamine agonist apomorphine caused a significant disruption in the control rats it did not further disrupt the existing deficit in the Ara-C treated rats. These data provide evidence to support the contention that modest neurodevelopmental insults can significantly affect sensorimotor gating processes in an adult onset dependent manner.

Methylation of trimethyltin compounds by estuarine sediments.

Both biologically active and autoclaved sediments convert trimethyltin hydroxide to the volatile tetramethyltin. Larger amounts of tetramethyltin were formed in the bioactive sediments than in the sterile sediments. No volatile tin compounds were detected in the absence of trimethyltin hydroxide or from trimethyltin hydroxide in seawater or in seawater containing bentonite. The formation of tetramethyltin is slow, taking over 80 days at 16 degrees C to reach a maximum. The extent of conversion, although significant, is not extensive. The formation of tetramethyltin occurs in estuarine sediments by both abiotic and biologically enhanced pathways. A redistribution mechanism accounts for at least the abiotic pathway and possibly both formation pathways.

Hormesis: a response to low environmental concentrations of petroleum hydrocarbons.

Crab zoeae (Rhithropanopeus harrisii) were exposed to water-soluble fractions of jet fuel (JP5) for the first 5 days or for the duration of zoeal development (11 to 14 days). Short-term exposure or continuous exposure to low concentrations of petroleum hydrocarbons caused no increase in mortality or changes in development rate, and increased megalopal weight was characteristic of such groups. This phenomenon, termed "hormesis," is probably a generalized aspect of environmental stress etiology but has seldom been reported as such.

Conversion of 2,4,6-trinitrophenol to a mutagen by Pseudomonas aeruginosa.

A strain of Pseudomonas aeruginosa reduced 2,4,6-trinitrophenol (picric acid) to 2-amino-4,6-dinitrophenol (picramic acid) under anaerobic conditions. Mutagenic assays of picric acid and picramic acid were carried out with histidine-requiring strains of Salmonella typhimurium. Picric acid (10 micrograms per plate) demonstrated mutagenicity (both frame shift and base substitution-gype mutations) only after activation with a rat liver homogenate preparation. Picramic acid (1 microgram per plate) induced both base pair substitution and frame shift-tupe mutations without activation by the rat liver preparation.