Inbred mouse strains differ in the regulation of startle and prepulse inhibition of the startle response.

The startle response and adaptability of the startle response (prepulse inhibition and habituation) have been observed in animals. The studies reported here screened 8 inbred mouse strains to determine whether genetic factors influence these behaviors. Strain differences were found in both the sensitivity to acoustic startle and the magnitude of both the auditory and tactile startle as well as the magnitude of prepulse inhibition (PPI) of both tactile and acoustic startle.

Pharmacological investigation of (+)- and (-)-cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo-[3,2-h]isoq uinoline, a bridged-nicotine analog.

We recently synthesized a bridged-nicotine (BN) analog and its enantiomers. They failed to compete for [3H]nicotine binding in rat brain homogenates, yet they produced nicotine-like effects by decreasing locomotor activity and producing antinociception in the tail-flick, hot-plate and PPQ tests in mice. Therefore, additional in vivo and in vitro studies were undertaken to determine whether these compounds are indeed acting independently of the nicotinic system.

Neurosteroids modulate nicotinic receptor function in mouse striatal and thalamic synaptosomes.

Progesterone and its A-ring reduced metabolites are allosteric activators of GABA(A) receptors. The studies reported here examined the effects of these steroids on brain nicotinic receptors using an 86Rb+ efflux assay that likely measures the function of alpha4beta2-type nicotinic receptors and [3H]dopamine release, which may be modulated by an alpha3-containing nicotinic receptor. Both of the A-ring reduced metabolites of progesterone were noncompetitive inhibitors of both assays, whereas progesterone inhibited only the 86Rb+ efflux assay.

Long-term ethanol and nicotine treatment elicit tolerance to ethanol.

Several previous studies have shown that 1 to 2 weeks of treatment with ethanol elicits tolerance to several effects produced by ethanol and cross-tolerance to nicotine-induced hypothermia. Similarly, short-term, high-dose nicotine treatment produces tolerance to nicotine and cross-tolerance to ethanol-induced hypothermia. In the studies reported here, C57BL/6 mice were force-fed ethanol, nicotine, or an ethanol/nicotine combination in the drinking water for 6 months.