Startle Modulation

► Prepulse Inhibition

A Word of History

Awareness of state dependence arose in seventeenth century popular and medical culture and concerned states of the internal, physiological, and mental milieu (Siegel 1985). Both that century's most acknowledged accounts and the first experimental investigation of state dependence (Girden and Culler 1937) involved states induced by drugs. Influentially capturing the perception of state dependence at that time, (Overton 1983) attributed state dependence to high, "toxic" doses of drugs; considered state dependence to be genuine only if bidirectional (i.e., if occurring upon both drug-to-placebo and placebo-to-drug changes of state); struggled with the issue as to whether state dependence requires that drug-to-placebo and placebo-to-drug state changes should produce symmetrical failures to remember; and argued on theoretical grounds that state dependence and ► drug discrimination are fundamentally similar. As will be apparent in the following lines, the state dependence concept has much evolved; how and when state dependence occurs has since been studied extensively in humans and animals in well-controlled experimental investigations in laboratory settings.

A Case of State Dependence

Studies of state dependence involve ► learning. The learning assays used may include single trials or multiple-trial learning opportunities, single or multiple-session classical conditioning, or acquisition of an appetitively or aversively motivated instrumental response. As in many ► memory researches, the key dependent variables assess the ability to remember, and recall is often measured operationally by the latency with which a remembered response occurs. The special issue of interest here about the functioning of memory is how memory may vary depending on the similarity or dissimilarity between the state that prevailed at the time of learning and the state that prevails at the time of recall. States thus constitute the independent variable. Failures of "transfer" of the ► engram, or memory trace, are said to occur when recall is hampered by a change of state.

Figure 1 offers an example of state dependence; here, rats are trained in 15 min sessions everyday to press a lever for food reward; every tenth lever press yields access to food (► fixed-ratio: 10, or FR10 schedule). The rat reaches the acquisition criterion when, on a given training session, it completes 10 lever presses within 120 s after the session begins. Two days later, in a test session, recall is measured by determining whether the animal again completes the first FR10 schedule within 120 s. Different groups of rats are trained with (i.e., before the training sessions receive an injection and thus are "under the influence of") either saline or one of different "training" doses of the benzodiazepine, ► chlordiazepoxide (CDP). Later, the rats are tested with (i.e., "under the influence of") either saline or one of different CDP "test" doses.

As shown in the left panel of Fig. 1, recall was perfect by rats that were both trained and tested with saline (points at "0") and by rats that acquired the response while treated with one CDP dose (0.16-40 mg/kg for different rats) and then tested with the same dose. However, as shown in the middle panel, rats trained with 0.1640 mg/kg doses of CDP and then tested with saline failed to recall in a manner that depended on the training dose, complete failure occurring with 40 mg/kg. Conversely (right panel), rats trained with saline and then tested with 0.16-160 mg/kg doses also failed to recall, now in a manner that varied with the CDP test dose. Thus, state dependence can occur with both drug-to-saline and

State Dependence of Memory. Fig. 1. Results of transfer tests in groups of rats that acquired an operant response in one pharmacological condition (i.e., saline or one of several doses of chlordiazepoxide(CDP) and were tested in either the same or another condition. Upper and lower abscissa: CDP dose at which the animals were trained and tested, respectively;0 refers to saline. Ordinate: percentage of rats (n = 7/group) that in test sessions completed the first FR10 schedule within 120 s. (Redrawn from Colpaert 1990.)

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Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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