Effects of phencyclidine on spatial learning and memory: nitric oxide-dependent mechanisms

• Cognitive deficits of schizophrenia constitute a disabling part of the disease predicting treatment success as well as functional outcome. Phencyclidine (PCP), a non-competitive NMDA receptor antagonist was used to model schizophrenic cognitive dysfunctions of learning and memory using the Morris water maze paradigm for reference memory. In experiment 1 male Sprauge-Dawley rats were acutely administered PCP (0.5, 1.0 and 2.0 mg/kg s.c.) before the first swim session on each of the four acquisition days. Probe test for reference memory was performed 2 days after the last acquisition day; the first probe without drug treatment to assess reference memory and a second probe with prior drug treatment to control for state dependency effects of PCP. In experiment 2 the effects of pre-treatment (10 min before PCP) with the nitric oxide synthase inhibitor, L-NAME (10 mg/kg s.c.), on the PCP (2 mg/kg)-induced spatial memory deficit was evaluated in the Morris water maze paradigm for reference memory. The results showed that PCP in a dose of 2 mg/kg disrupts spatial learning as estimated by prolonged search time to find platform during acquisition as well as the reference memory test as measured by less time spent in target quadrant during probe trial. No state dependency effects of PCP were found. Pre-treatment with L-NAME completely reversed the PCP-induced disruption of acquisition learning. The reference memory disruption was, however, not completely restored as measured by probe trial.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

Nyckelord

Analysis of Variance

Animals

Discrimination Learning/drug effects/physiology

Dose-Response Relationship

Drug

Enzyme Inhibitors/administration & dosage/*pharmacology

Hallucinogens/administration & dosage/*pharmacology

Male

Maze Learning/*drug effects/physiology

Memory/drug effects/physiology

NG-Nitroarginine Methyl Ester/pharmacology

Nitric Oxide/*metabolism

Nitric Oxide Synthase/drug effects/metabolism

Phencyclidine/administration & dosage/*pharmacology

Rats

Rats

Sprague-Dawley

Receptors

N-Methyl-D-Aspartate/agonists

Retention (Psychology)/*drug effects/physiology

Space Perception/drug effects/physiology

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)