effects of d-amphetamine and haloperidol on latent inhibition in healthy male volunteers

Abstract

Latent inhibition (LI) refers to a retardation of learning about the consequences of a stimulus when that stimulus has been passively presented a number of times without reinforcement. Acute positive-symptom schizophrenics, normal volunteers who score high on questionnaire measures of schizotypy and non-patients or animals treated with dopamine agonists show reduced LI. Neuroleptic drugs, such as haloperidol, administered at low doses, potentiate LI and effectively reverse disruption of LI induced by dopamine agonists in animals. However, a high dose of haloperidol, administered on its own, has been found to reduce LI. We examined the effects on LI of acute oral administration of an indirect dopamine-agonist, d-amphetamine (5 mg), and a nonselective dopamine receptor antagonist, haloperidol (5 mg), in normal male volunteers, using an associative learning task. Replicating previous reports, we found that d-amphetamine reduced LI; haloperidol also reduced LI, but only in subjects who scored low on the Psychoticism scale of the Eysenck Personality Questionnaire. In a subsequent study, no effect was found of 2 mg oral haloperidol administration on LI. The effect of 5 mg haloperidol on LI is interpreted as similar to that observed with a high dose of haloperidol in rats.

Dopamine, Paranormal Belief, and the Detection of Meaningful Stimuli

“…The lower sensitivity in the levodopa than placebo group was dependent on participantsʼ paranormal belief. Links between the emergence of paranormal belief and the DA system have been suggested (Brugger & Graves, 1997a) and tested (Mohr et al, 2004;Kumari et al, 1999). Here, contrary to our expectation, a reduced sensitivity in the levodopa as compared to the placebo group was only evident in the skeptics.…”

A pre-clinical study showing how dopaminergic drugs administered during pre-exposure can impair or facilitate latent inhibition

“…In humans, similar results have been reported for amphetamine (Gray et al 1992;Thornton et al 1996;Kumari et al 1999), nicotine (Allan et al 1995, and haloperidol (Williams et al 1996(Williams et al , 1997. In addition to these "typical" data, nicotine can facilitate (Rochford et al 1996) and haloperidol can impair (Buhusi et al 1999) LI.…”

Levodopa reverses gait asymmetries related to anhedonia and magical ideation

“…This approach would also offer a possibility to test for drug actions in unmedicated healthy but "psychosis-prone" subjects. It has, however, received surprisingly little direct (Kumari et al 1999;Williams et al 1997) and indirect (Gray et al 2002;Kopp et al 2002) attention. In particular, the neurotransmitter dopamine (DA) is an excellent candidate for such an approach.…”

“…Ever since the discovery that DA antagonists ameliorate acute psychotic symptoms (e. g., Klein and Davis 1969;Matthysse 1973), it has been accepted that this neurotransmitter plays a major role in the pathophysiology of schizophrenia (Laruelle and Abi-Dargham 1999 Pickar et al 1984) and schizotypal personality disorder (Siever et al 1991(Siever et al , 1993. Although the role of DA for even mild forms of schizotypy was emphasized (Mohr et al 2003a; Brugger and Graves 1997; Gray et al 2002;Kopp et al 2002), direct relationships between schizotypy and the DA system have rarely been investigated (Kumari et al 1999;Williams et al 1997).…”