Passive avoidance

One of the simplest procedures for looking for adverse effects on learning and memory is the so-called one-trial passive avoidance task [15]. There are several variants of this procedure, but the basic principal is that a rat or a mouse receives an aversive stimulation in the recognizable environment and on a later occasion shows it has remembered by not going there (passive avoidance). For example, a rat placed into the lit compartment of a two-compartment box will explore the apparatus and eventually enter 

---

The tests generally involve some form of maze but the simplest is the passive avoidance test. In this the animal learns that in a certain environment it will be punished with an electric shock for some particular action, like stepping onto a special part of the floor of the test chamber. The test of memory is how long the rat avoids (remains passive to) making the movement that will initiate the shock. Of course, drugs that reduce the animal s anxiety also modify the response. Using a maze in its simplest T shape, the animal is placed at the base of the vertical arm and a food reward at the end of one of the horizontal arms. Clearly the animal has to learn which arm contains the reward. Memory is assessed by the time taken for a food-deprived animal to reach the reward and the number of false arm entries. This simple system can be made more complex by introducing many more arms and branches but the principle is the same. 

ADHD Passive avoidance in spontaneously hypertensive rats Improves cognitive performance [57]... 

Both the M2 and M4 receptors are, as indicated above, coupled to Gj pathways and appear to mediate similar responses. The M2 receptor is widely expressed in the CNS but also present in heart and smooth muscle, while M4 is preferentially expressed in the CNS, especially in forebrain. Ablation of the M2 receptor leads to complete loss of muscarinic-agonist-stimulated bradycardia [55]. In the CNS, deletion of the M2 receptor abolishes oxotremorine induced akinesia and tremors [56]. Memory and learning tasks including passive avoidance and working memory are impaired in M2-receptor knockout mice, and there is decreased LTP in hippocampal slices [12],... 

There is not a consensus about the procedures to use to test for effects on learning and memory. The two most commonly used techniques are the water-filled maze, which is preferred for measuring learning, and passive avoidance, which is preferred for measuring memory (see Buelke-Sam et al., 1985). Retention is tested in a repeat test conducted approximately 1 week later. 

Mactutus CF, Unger KL, Tilson HA. 1982. Neonatal chlordecone exposure impairs early learning and memory in the rat on a multiple measure passive avoidance task. Neurotoxicology 3(2) 27-44. 

Costa LG, Murphy SD. 1982. Passive avoidance retention in mice tolerant to the organophosphorus insecticide disulfoton. Toxicol Appl Pharmacol 65 451-458. 

Passive avoidance task Morris water maze radial maze operant behavior tasks... 

Bammer, C., Pharmacological investigations of neurotransmitter involvement in passive avoidance responding a review and some new results, Neurosci. Biobehav. Rev., 6,247-296,1982. 

An acute dose of lobeline impairs attention in one animal model, but not as much as mecamylamine (Turchi et al. 1995). Lobeline improves memory when administered after a passive avoidance paradigm (Decker et al. 1993). Pretreatment with lobeline improves performance in rats with septal lesions on a spatial discrimination water maze. Lobeline is about one-tenth as potent as nicotine in the passive avoidance memory task, but equivalent to nicotine in the water maze. 

Ginseng extract improves the spatial learning performance of aged rats in an eight-arm radial maze and operant discrimination task (Nitta et al. 1995). It also improves memory performance in active-avoidance (shuttle-box) and passive-avoidance (step-down) tasks, and reinforces staircase-maze learning in both young and aged rats. (Petkov and Mosharrof 1987 Petkov et al. 1990 Petkov et al. 1992). The effects were also very dose dependent, with inverted U-shape dose-response curves. 

Several studies have looked at the effects of combined preparations that include ginseng. A preparation of Biota orientalis, Panax ginseng, and Schisandra chinensis (S-113 m) improved memory retention in a passive-avoidance task with senescence-accelerated mice (Nishiyama et al. 1996). This combination also reduced memory impairments induced by ethanol and scopolamine in the step-down test and electroconvulsive shock-induced memory impairment (Nishiyama et al. 1995). 

Delagarza VW. (1998). New drugs for Alzheimer s disease. Am Fam Physician. 58(5) 1175-82. DeNoble VJ, Repetti SJ, Geipke LW, Wood LM, Keim KL. (1986). Vinpocetine nootropic effects on scopolamine-induced and hypoxia-induced retrieval deficits of a step-through passive avoidance response in rats. Pharmacol Biochem Behav. 24(4) 1123-28. 

Lasarova MB, Mosharrof AH, Petkov VD, Markovska VL, Petkov W. (1987). Effect of piracetam and of standardized ginseng extract on the electroconvulsive shock-induced memory disturbances in "step-down" passive avoidance. Acta Physiol Pharmacol Bulg. 13(2) 11-17. 

Stoll S, Scheuer K, Pohl 0, Muller WE. (1996). Ginkgo biloba extract (EGb 761) independently improves changes in passive avoidance learning and brain membrane fluidity in the aging mouse. Pharmacopsychiatry. 29(4) 144-49. 

Adolescent nicotine exposure results in pronounced and persistent nicotinic cholinergic receptor upregulation in male rats and hippocampal cell damage in females (Trauth et al. 1999). During and following nicotine treatment as adolescents, female rats show impaired rearing and locomotor activity, whereas males are unaffected. On the other hand, improved performance was observed in passive avoidance (Trauth et al. 2000). 

Riekkinen PJ, Sirvid J, Riekkinen M, Lammintausta R, Riekkinen P (1992) Atipame-zole, an antagonist, stabilizes age-related high-voltage spindle and passive avoidance defects. Pharmacol Biochem Behav 41 611-614 Rohrer DK (1998) Physiological consequences of P-adrenergic receptor disruption. J Mol Med 76 764-772... 

---