Choosing the best genetic strains of mice for developing a new knockout or transgenic mouse requires extensive knowledge of the endogenous traits of inbred strains. Background genes from the parental strains may interact with the mutated gene, in a manner which could severely compromise the interpretation of the mutant phenotype. The present overview summarizes the literature on a wide variety of behavioral traits for the 129, C57BL/6, DBA/2, and many other inbred strains of mice. Strain distributions are described for open field activity, learning and memory tasks, aggression, sexual and parental behaviors, acoustic startle and prepulse inhibition, and the behavioral actions of ethanol, nicotine, cocaine, opiates, antipsychotics, and anxiolytics. Using the referenced information, molecular geneticists can choose optimal parental strains of mice, and perhaps develop new embryonic stem cell progenitors, for new knockouts and transgenics to investigate gene function, and to serve as animal models in the development of novel therapeutics for human genetic diseases.

Morphine produces analgesia at opiate receptors expressed in nociceptive circuits. , ␦, and opiate receptor subtypes are expressed in circuits that can modulate nociception and receive inputs from endogenous opioid neuropeptide ligands. The roles played by each receptor subtype in nociceptive processing in drug-free and morphine-treated states have not been clear, however. We produced homologous, recombinant , opiate receptor, heterozygous and homozygous knockout animals that displayed Ϸ54% and 0% of wild-type levels of receptor expression, respectively. These mice expressed receptors and ␦ receptors at near wild-type levels. Untreated knockout mice displayed shorter latencies on tail f lick and hot plate tests for spinal and supraspinal nociceptive responses than wild-type mice. These findings support a significant role for endogenous opioid-peptide interactions with opiate receptors in normal nociceptive processing. Morphine failed to significantly reduce nociceptive responses in hot plate or tail f lick tests of homozygous receptor knockout mice, and heterozygote mice displayed right and downward shifts in morphine analgesia dose-effect relationships. These results implicate endogenous opioidpeptide actions at opiate receptors in several tests of nociceptive responsiveness and support receptor mediation of morphine-induced analgesia in tests of spinal and supraspinal analgesia.Morphine acts at seven transmembrane domain, G proteinlinked receptor products of genes encoding , , and ␦ opiate receptor subtypes (1-9). Each of these genes is expressed in neurons in several neuronal circuits implicated in nociception (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20).receptor mediation of much morphine-induced analgesia has been postulated (21, 22). However, studies using compounds with relative preferences for ␦ and receptors have suggested that these other two opiate receptor subtypes also might play significant roles in the analgesic responses induced by morphine-like drugs (22-26). The extent to which each of the three opiate receptor subtype gene products might participate in different features of opiate-or morphineinduced analgesia thus has remained unclear. Elucidation of the selective analgesic contributions of each opiate receptor subtype is of substantial potential importance for developing improved analgesic medications with minimal undesirable effects.Expression of endogenous opioid-peptide agonists, especially those derived from the preproenkephalin and preprodynorphin genes, in circuits associated with pain perception suggests that opioid-peptide interactions with opiate receptors could be well positioned to modulate nociceptive responses in the absence of exogenously administered opiate drugs (10,12,14,(27)(28)(29)(30)(31)(32). Studies of pain responses in animals and humans treated with opiate antagonists, however, have documented modifications in nociception in some but not all studies (33,34). These results also have left uncertainty about the power of endogenous opioid-peptide interactions with ...

The brain vesicular monoamine transporter (VMAT2) pumps monoamine neurotransmitters and Parkinsonism-inducing dopamine neurotoxins such as 1-methyl-4-phenyl-phenypyridinium (MPP ؉ ) from neuronal cytoplasm into synaptic vesicles, from which amphetamines cause their release. Amphetamines and MPP ؉ each also act at nonvesicular sites, providing current uncertainties about the contributions of vesicular actions to their in vivo effects. To assess vesicular contributions to amphetamine-induced locomotion, amphetamine-induced reward, and sequestration and resistance to dopaminergic neurotoxins, we have constructed transgenic VMAT2 knockout mice. Heterozygous VMAT2 knockouts are viable into adult life and display VMAT2 levels one-half that of wild-type values, accompanied by smaller changes in monoaminergic markers, heart rate, and blood pressure. Weight gain, fertility, habituation, passive avoidance, and locomotor activities are similar to wild-type littermates. In these heterozygotes, amphetamine produces enhanced locomotion but diminished behavioral reward, as measured by conditioned place preference. Administration of the MPP ؉ precursor N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to heterozygotes produces more than twice the dopamine cell losses found in wild-type mice. These mice provide novel information about the contributions of synaptic vesicular actions of monoaminergic drugs and neurotoxins and suggest that intact synaptic vesicle function may contribute more to amphetamine-conditioned reward than to amphetamine-induced locomotion.