Behaviour agonistic

There is no reason why DA receptor block should not occur as soon as the antagonist reaches the brain. Antagonism of DA agonist-induced behavioural or electrophysiological... 

The 5-HT3 receptor is found appropriately in mesocortical areas and while behavioural studies with their antagonists in rodents showed potential antipsychotic activity, they have proved ineffective in patients. 5-HTia agonists may be more useful. They have been found to increase the extracellular concentration of DA in the frontal cortex of rats but diminish apomorphine-induced stereotypy (striatal effect). So they could be of some benefit, especially against negative symptoms, without causing EPSPs (see Chapter 9). 

Beckett, S and Marsden, CA (1997) The effect of central and systemic injection of the 5-HTia receptor agonist 8-OHDPAT and the 5-HTia receptor antagonist WAY100635 on peri-aquaductal grey-induced defence behaviour. J. Psychopharmacol. 11 35 0. 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

One of the conspicuous resorcinols is HU-308 (362), which is a CB2-specific agonist this compound does not bind to CBi (if > 10 uM), but has a significant affinity for CB2 ( i = 22.7 nM) [226]. HU-308 elicited analgesic activity in a formalin-induced peripheral pain model and an anti-infiam-matory effect on arachidonic acid-induced ear inflammation, though it showed no activity in a tetrad of behavioural tests, which are linked to CNS activity (Table 6.34). 

Luiten G.M., Koolhaas J.M., de Boer S. and Koopmans S.J. (1985). The cortico-medial amygdala in the central nervous system organisation of agonistic behaviour. Brain Res 332, 283-297. 

P Hess, JB Lansman, RW Tsien. (1984). Different modes of Ca channel gating behaviour favoured by dihydropyridine Ca agonists and antagonists. Nature 311 538-544. 

Pilla M., Perachon S., Sautel F. et al. Selective inhibition of cocaine-seeking behaviour by a partial dopamine D3 receptor agonist. Nature. 400 371, 1999. 

Cowen, P. J., Grahame-Smith, D. G., Green, A. R., and Heal, D. J. (1982) Beta-adrenoceptor agonists enhance 5-hydroxytryptamine-mediated behavioural responses. Br. J. Pharmacol.. 76 265-270. 

Unilateral lesions can be obtained through different means hemisection, 6-OH-DA and MPTP injections. Supersensitivity is developed at the postsynaptic receptors on the lesioned side, giving rise to an asymmetry in the animals treated. Administration of a DA agonist to a lesioned animal will give rise to a rotating behaviour [51]. 

A 5-HTlA receptor agonist will be identified in this model as a compound which induces the 5-HT behavioural syndrome (fiat body posture, abducted hind and forelegs and forepaw treading). In addition, an a-adren-ergic agonist induces piloerection in the reserpinized rat. 

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