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16: Experiments with amphetamine and neurotoxins.

6-hydroxydopamine (6-OHDA) is a neurotoxin, which kills dopaminergic and noradrenergic (or norepinephrinic) neurons. This substance is therefore ideal if the purpose is to induce specific lesions. Using 6-OHDA in C. putamen and N. accumbens resulted in the following observations:

* Caudatus putamen + 6-OHDA + Amphetamine (systemic injections) => Considerably increased locomotion and no stereotypies.

* Nucleus accumbens + 6-OHDA + Amphetamine (systemic injections) => No locomotion but stereotypic behaviours.

First of all, these results suggested that C. putamen seems to influence the stereotypic response towards Amphetamine while N. accumbens dealt with the locomotoric response.

Secondly, the observation that the locomotoric response was considerably enhanced (relative to the response observed if only Amphetamine was injected) suggests that the stereotypic response somehow compete with the locomotoric response. It is probably at this point that the possibility for N. accumbens to moderate the activity in C. putamen is significant.

* Other experiments using injections of Amphetamine directly into C. putamen did not result in the same complete repertoire of stereotypies, which normally was a consequence of systemic injections of Amphetamine, suggesting that other brain structures could be involved in the stereotypic response. To further complicate matters it has turned out that the longer away from the brain these injections take place, the more moderating factors can play a part. To give an example, rats display different types of stereotypies as a response dependant of whether the injections was carried out in the hind legs or in the neck region.

Researchers using humans have observed that neuroleptica shows a strong correlation between the therapeutic effect and the ability to block Dopamine receptors in the brain and the ability to counteract, or neutralize, amphetamine-induced stereotypies.

Many observations therefore seem to hint at an increased dopamine secretion in certain brain areas as causative for stereotypies, but the subject is highly complex.

To touch upon the subject of stereotyping bank voles it would at present seem as if their stereotypies are more connected to the level of another neurotransmitter, 5-hydroxytryptamine (Serotonin) - see "Female Bank voles as potential new animal models for Depression and General Anxiety Disorder (GAD)".

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