Non-genetic factors that influence methamphetamine intake in a genetic model of differential methamphetamine consumption.

RATIONALE: Genetic and non-genetic factors influence substance use disorders. Our previous work in genetic mouse models focused on genetic factors that influence methamphetamine (MA) intake. The current research examined several non-genetic factors for their potential influence on this trait. OBJECTIVES: We examined the impact on MA intake of several non-genetic factors, including MA access schedule, prior forced MA exposure, concomitant ethanol (EtOH) access, and gamma-aminobutyric acid type B (GABAB) receptor activation. Selectively bred MA high drinking (MAHDR) and low drinking (MALDR) mice participated in this research. RESULTS: MAHDR, but not MALDR, mice increased MA intake when given intermittent access, compared with continuous access, with a water choice under both schedules. MA intake was not altered by previous exposure to forced MA consumption. Male MAHDR mice given simultaneous access to MA, EtOH, and an EtOH+MA mixture exhibited a strong preference for MA over EtOH and EtOH+MA; MA intake was not affected by EtOH in female MAHDR mice. When independent MAHDR groups were given access to MA, EtOH, or EtOH+MA vs. water in each case, MA intake was reduced in the water vs. EtOH+MA group, compared with the water vs. MA group. The GABAB receptor agonist R(+)-baclofen (BAC) not only reduced MA intake but also reduced water intake and locomotor activity in MAHDR mice. There was a residual effect of BAC, such that MA intake was increased after termination of BAC treatment. CONCLUSIONS: These findings demonstrate that voluntary MA intake in MAHDR mice is influenced by non-genetic factors related to MA access schedule and co-morbid EtOH exposure.

An economic and technical assessment of the use of plant cell cultures for natural product synthesis on an industrial scale.

Plant cell cultures may be used as an alternative source of established natural products, as a source of novel 'lead' compounds or as a source of enzymes for modification of precursors. Only a few plant cell processes are operating commercially and their performance characteristics are industrial secrets. The economic aspects of natural product synthesis in plant cell cultures are presented on the basis of data derived from work on a pilot plant with bioreactors of 5-80 litres in which cells are grown in batch liquid culture. Cost analysis shows that the labour costs of operating plant cell culture processes are much higher than those for microbial processes, which reflects the longer process times of plant systems. These can be reduced by increasing the cell growth rate, the biomass yield and/or the product yield. Higher yields can be obtained by optimizing media conditions, but there are no standard guidelines for this. Each system has to be developed individually. Reducing the number of production runs a year, usually by increasing the number of days for which each batch of cells is synthesizing product, can markedly decrease costs. Economic assessment of the viability of production in plant cell cultures must consider not only production costs but also the expected market price of the product and the volume of sales.