Cognitive enhancers prevent the hypoxia‐induced disruption of conditioned avoidance response

Abstract

AbstractSix cognitive enhancer compounds, the new class of central nervous system (CNS)‐active drugs (vinpocetine, vincamine, dihydroergotoxine, nicergoline, piracetam, and meclofenoxate) were tested before acquired two‐way active avoidance response of spontaneously hypertensive (SH) rats had been disrupted by lowered environmental oxygen concentration (6% oxygen). Exposure to normobaric hypoxia reduced the number of conditioned avoidance responses (CAR) by 44%; at the same time the spontaneous locomotor activity of the animals (measured by the alteration in the number of intertrial crossings) was not considerably decreased, and latency times of conditioned responses were not lengthened significantly. The compounds tested showed protective effect against hypoxia‐induced performance deficit without stimulating spontaneous activity. Vinpocetine antagonized nearly completely CAR blockade in the 1.25‐5.0 mg/kg p.o. dose range, restoring the ratio of avoidance responses to normal level. Vincamine exerted activity at a dose of 20 mg/kg p.o. Dihydroergotoxine and nicergoline were effective at 10 mg/kg p.o., Piracetam and meclofenoxate showed moderate protective activity at 2,000 and 500 mg/kg p.o., respectively. For comparison, the effect of dopaminergic drugs of a different mechanism of action (amphetamine, apomorphine, bromocriptine, and methylphenidate) was also tested in a similar situation. Only amphetamine (at 1.0 mg/kg i.p.) and low doses of apomorphine (0.1 and 1.0 mg/kg) had a favorable effect against hypoxia‐induced CAR blockade; this effect was accompanied by an increase in locomotor activity. On the basis of these data, the relatively simple behavioral method applied by us, protection of acquired conditioned response against the disruptive effect of hypoxia in SH rats, seems suitable to detect nootropic activity.