Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis

@article{MaronaLewicka2005DistinctTP,
  title={Distinct temporal phases in the behavioral pharmacology of LSD: dopamine D2 receptor-mediated effects in the rat and implications for psychosis},
  author={Danuta Marona-Lewicka and Ronald A. Thisted and David E. Nichols},
  journal={Psychopharmacology},
  year={2005},
  volume={180},
  pages={427-435}
}
RationaleThe effect of LSD in humans has been described as occurring in two temporal phases. The behavioral effects in rats also occur in two temporal phases: an initial suppression of exploration followed by increased locomotor activity.ObjectivesWe decided to investigate this phenomenon from the perspective that the pharmacology might have relevance to the neurochemical mechanisms underlying psychosis.MethodsTwenty-five male Sprague–Dawley rats were trained to discriminate LSD (186 nmol/kg, 0… 

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References

SHOWING 1-10 OF 52 REFERENCES

Dissociation of multiple effects of acute LSD on exploratory behavior in rats by ritanserin and propranolol

It is suggested that the initial suppressive effects of LSD in the BPM paradigm are dissociable from the subsequent increases in locomotion and that the two effects are mediated via different serotonergic orβ-adrenergic receptors.

The discriminative stimulus properties of LSD: Mechanisms of action

A proposed animal model for hallucinogens based on LSD's effects on patterns of exploration in rats.

The possibility that LSD's enhancement of neophobia in rats may be a valid analogue model of its intensification of affective reactions in humans is discussed.

Characterization of the discriminative stimulus properties of centrally administered (−)-DOM and LSD

A characterization of LSD-antagonist effects of pirenperone in the rat

Effects of 5HT-1A agonists on locomotor and investigatory behaviors in rats differ from those of hallucinogens

5HT-1A agonists have a different profile of behavioral effects than 5HT-2 agonists and that the two classes of drugs can be differentiated using the same test paradigm, providing further support for the hypothesis that the previously described potentiation of neophobia induced by hallucinogens is due to the activation of 5 HT-2 receptors.

Risperidone (R 64 766), a potent and complete LSD antagonist in drug discrimination by rats

Based on the pharmacological profile of risperidone and the other LSD antagonists, it was concluded that a potent central 5-HT2 and catecholamine antagonism is needed for a potent and complete antagonism of the 0.16 mg/kg LSD-cue.

LSD and structural analogs: pharmacological evaluation at D1 dopamine receptors

The present study investigated the binding and functional properties of LSD and several lysergamide analogs at dopamine D1 and D2 receptors, and provided a basis for evaluating the contribution of D1 receptors to the biobehavioral actions of LSD.

5-HT2A/2C receptor agonists potentiate the discriminative cue of (+)-amphetamine in the rat

Differentiation between the stimulus effects of l-5-hydroxytryptophan and LSD.

...