An mTph2 SNP gives rise to alterations in extracellular 5-HT levels, but not in performance on a delayed-reinforcement task.

5-Hydroxytryptamine (5-HT) is an important neurotransmitter mediating many aspects of cognition and behaviour. One psychology in which 5-HT plays an important role is impulsive responding. Recently, we have demonstrated that variation in an aspect of impulsive behaviour, namely delayed gratification, has a clear genetic contribution. Here, we examined the neurobiological relevance of a recently discovered single nucleotide polymorphism (SNP) in the murine gene tryptophan hydroxylase (mTph2) by analysing extracellular levels of 5-HT in medial prefrontal cortex (mPFC) and ventral striatum (VS), key brain regions for impulsive behaviours. The allelic variants were associated with systematic effects on baseline 5-HT efflux in the mPFC and VS. We then went on to examine whether the mTph2 allelic variants gave rise to differences in impulsive behaviour. However, the mTph2 genotype, and therefore presumably baseline brain levels of 5-HT, did not predict impulsive choice, as indexed by sensitivity to delayed reinforcement. Consequently, the data do not support a role for the mTph2 C1473G polymorphism on this aspect of impulsive behaviour. Instead, they indicate that perturbations of the 5-HT system via heritable traits may have differential consequences for qualitatively distinct aspects of impulsive behaviour.

Effect of acute ozone exposure on locomotor behavior and striatal function.

Ozone exposure, depending on the dose, is a noninvasive model of oxidative stress. The purpose of this work was to study striatal damage and cell death induced by oxidative stress. Sixty-three male Wistar rats were divided into two groups--Group 1: animals were exposed to an air stream free of ozone for 4 h; and Group 2: animals were exposed to 1 ppm of ozone for 4 h. Four subgroups in each treatment group were then tested 3 h after control or ozone exposure for: (1) exploratory and freezing behavior; (2) lipid peroxidation levels; (3) in vivo release of amino acid and monoamine transmitters, and metabolites and nitric oxide; and (4) striatal ultrastructural changes. Results showed that the ozone decreased exploratory and increased freezing behaviors. It also increased striatal lipoperoxidation levels and basal dopamine, glutamate, and nitric oxide (arginine, citrulline, and nitrate used as indices) concentrations and decreased those of 5-HT. Concentrations of GABA were initially decreased 3 h after ozone but then were increased 3 and 5 days afterwards. Increased lipofucsine, neuronal cytoplasm and dendrite vacuolation, and dilation of rough endoplasmic reticulum cisterns and dark cells were observed in striatal medium spiny neurons in ozone-exposed rats. These alterations suggest a neurodegenerative process caused by oxidative stress after acute ozone exposure.

Biphasic role of dopamine on female sexual behaviour via D2 receptors in the mediobasal hypothalamus.

Dopamine has been implicated in the control of sexual behaviour, but its role seems quite complex and controversial. The aim of the present experiments was to investigate the effects of dopamine (DA) acting on D2 receptors in the mediobasal hypothalamus (MBH) on sexual behaviour in female sheep. To achieve this, the D2 agonist, quinpirole, was administered bilaterally via microdialysis probes into the MBH of ovariectomized ewes either before or after oestradiol (E2) administration. Quinpirole (100 ng/ml) infused for 6 h just before E2 hastened the onset of oestrus behaviour and the luteinizing hormone surge, whereas the same treatment given 6-12 h or 18-21 h after E2 decreased the intensity of sexual receptivity without affecting LH or prolactin secretion. We then tested the hypothesis that E2 stimulates the onset of oestrus partly by decreasing DA activation of D2 receptors. In this case the D2 antagonists pimozide or spiperone (100 ng/ml) were infused into the MBH via microdialysis probes for 11 h in the absence of E2 administration. A significant number of ewes showed induction of receptivity with both antagonists, although its intensity was significantly lower than that induced by E2. These treatments generally did not significantly alter extracellular concentrations of monoamines or aminoacids although quinpirole modulated the ability of sexual interactions to increase noradrenaline release. These experiments show that DA acts via D2 receptors in the MBH to control female sexual behaviour in a biphasic manner: the onset of sexual motivation and receptivity requiring an initial increase in activation followed by a decrease. This dual action could explain some of the controversies concerning DA action on sexual behaviour.