The increase in responsiveness due to a strong, usually painful stimulus.
Sensitization is a non-associative learning process that leads to increased responsiveness to a stimulus and is considered complementary to habituation. The increase in responsiveness or behavior is due to the exposure of a strong, most commonly noxious, stimulus that is causing pain. It is therefore logical to infer that sensitization’s adaptive value is high, as it protects an organism from predators and other potential dangers Eisenstein, Eisenstein, Smith (2001).
The most prominent non-associative learning theory was composed by Groves and Thompson (1970). Neurophysiological concepts were combined with concerns of human ethology and evolution to create the “dual process” theory. The dual process theory was the one which took into consideration both sensitization and habituation. This theory advocated that repeated stimulation would produce two independent processes that could both be active at the same time: decreased responsiveness (habituation) or increased responsiveness (sensitization). The authors believed that the two processes take place in different parts of the nervous system. Habituation is believed to take place in the so-called S-R system (reflex arc) that controls reflexes, whereas sensitization is believed to occur in the “state system” which is responsible for the level of readiness to respond. The state system requires arousal to become activated, while the S-R system is activated with the presentation of an eliciting stimulus. Further, habituation is thought to be stimulus-specific and involves learning, in contrast to sensitization which is not highly specific and does not require learning. However both are of relative permanence; they are expected to decay at the absence of stimulation. More characteristics of sensitization are presented below.
Characteristics of Sensitization
Sensitization occurs in the “state” system and not in the “S-R” system.
During habituation training, sensitization appears initially but then deteriorates.
The amount and duration of sensitization are directly related to stimulus intensity. At high intensities, sensitization is directly related to stimulus intensity and frequency. However, at low intensities there may be little or no sensitization.
Sensitization decays spontaneously as soon as the sensitizing stimulus has stopped.
Repeated presentations of a sensitization stimulus result in gradual reduction of sensitization.
Response sensitization displays generalization.
Dishabituation is considered as an instance of sensitization.
Temporal conditioning of sensitization may occur.
Sensitization has not received as much attention as habituation did; however especially enlightening was the study of the neurophysiological basis of sensitization, in laboratory settings, with the mollusk Aplysia and the work of Kandel, as well as with the work of others scholars on kindling and long-term potentiation.
Sensitization and long-term potentiation are similar processes but differ in their site of application. Sensitization occurs in specific pathways (state), while long-term potentiation occurs in synapses. However, the process of sensitization involves the mechanism of long-term potentiation.
Long-term potentiation of synaptic transmission is a major mechanism for investigating learning and memory in the synaptic level. Long-term potentiation is found in several regions of the brain, with the most prominent being the hippocampus thus its obvious involvement in the neural basis of some forms of memory Cooke & Bliss (2006). It is a form of synaptic plasticity and is defined as a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse.
High-frequency stimulation causes an increase in the efficiency of synaptic transmission, therefore enhancing the efficiency of the signal. For the induction of long-term potentiation, the activation of excitatory receptors is required Cooke & Bliss (2006). Bliss and Collingridge (1993) reported on the properties of long-term potentiation that differentiates it from other forms of synaptic plasticity: input specificity (it does not spread to other synapses), associativity (when a weak input of a single pathway is insufficient for the induction of long-term potentiation, simultaneous strong stimulation of another pathway can potentiate the weak stimulation), and cooperativity (apart from strong stimulation, long-term potentiation can be induced by the cooperation of many yet weaker stimulations). Since long-term potentiation occurs when a neuron shows an increased excitability over time due to a repeated behavior and the heightened synaptic transmission leads to the amplification of responses (i.e., pain), its involvement with the process of sensitization is high.
While the long-term potentiation of synapses in localized cell tissues seems to provide an elegant substrate for learning and memory, researchers turn their attention into experimentations with the whole living organism (in vivo experiments). Morris and colleagues (1986) provided for the first time some data from in vivo experiments in which it was indicated that long-term potentiation was essential for the construction of memories. Using rats, Morris and colleagues were able to examine their spatial memory by inserting an N-methyl-D-aspartate (NMDA) blocker drug in their hippocampus, a brain structure implicated in learning. NMDA is a glutamate receptor and an ion channel protein within nerve cells, and it is responsible for the control of synaptic plasticity and memory function. Initially rats were trained to swim in a water maze, in order to find the platform hidden beneath (in the center and the sides of the pool) and escape. As soon as the rats were able to locate the platform, they were separated in two groups. One group constituted the control group, while rats of the second group received the drug that blocks NMDA. Then both groups of rats were exposed to the water maze spatial memory task with the rats of the control group being successful in locating the platform and escaping the pool. Contrary, the second group of rats exhibited impaired performance, as long-term potentiation could not be induced indicating thus damage in the hippocampus. This series of experiments indicated that long-term potentiation is implicated in learning and memory processes. Finally, dysfunctions in the process of long-term potentiation are thought to be implicated in mood disorders Post (2007) and neurodegenerative diseases as Parkinson’s Cooke & Bliss (2006). Long-term potentiation is a fundamental process in a cellular level with implications in the process of learning.
Both sensitization and kindling are forms of learning occurring in some parts of the nervous system, and the common characteristic they exhibit is the increase in responsiveness. Kindling can be thought of as a specific type of sensitization.
Kindling became known to the scientific world in the late 1960s through the published work of Goddard (1967) on the neurobiology of learning and later after the application of Goddard’s model on the study of epilepsy. Goddard (1967) runs a series of experiments on rats where, in order to investigate their abilities to learn tasks, he administered electrical stimulations in various regions of their brains. With daily repetition of the electrical stimuli, the rats began seizing. That response, however, was astonishing, as the administered stimuli were too low to induce seizures. Even more surprising was the final observation of the rats having unprovoked seizures, that is, seizing without stimulation. In sensitization repetitive stimulation produces a full response. A full response can be elicited even with lower stimulus levels than the original stimulus. It appears that a decrease in the threshold of excitability develops leading to the automatic occurrence of the response, without external stimulation. Eventually, with further repetition, the response occurs spontaneously, in the absence of any stimulus demonstrating thus the phenomenon of kindling. The changes caused by kindling seem to be long-term, but they are not permanent.
Kindling is universal across species (from frogs to humans) and throughout the brain, and it was the first neuroplasticity phenomenon suggested to give information on memory processes. At a first glance, it may seems awkward to imply that epileptic seizure activity could be interconnected learning; yet, it is plausible that the diverse mechanisms constituting kindling and learning interconnect and share several common mechanisms. In effect, under this conceptualization, both kindling and learning can potentially be considered as phenomena of neuroplasticity. However when kindling was compared to long-term potentiation as to which neuroplasticity phenomenon was more appropriate for modelling memory processes, long-term potentiation appeared to dominate, mostly because long-term potentiation was observed under normal neural activity contrary to kindling that was observed under seizures.
Further, kindling constitutes the model for the development or recurrence of medical (epilepsy) and psychiatric illnesses such as addictions and mood disorders, in which pathologies’ recurrence is inherent Post (2007). Goddard’s model has been referred to as the “kindling model for epileptogenesis” as it is the most frequently used model for temporal lobe epilepsy with complex partial seizures. It is used by scientists to study the effects of repeated seizures on the brain. What was demonstrated in the experiments with rats, the same applies for humans; a seizure may raise the possibility that more seizures will occur since repeated stimulation “lowers the threshold” and paves the way for seizures to reoccur (Dennison, Teskey, Cain, 1995, Racine, 1978). In an attempt to better understand the occurrence of epileptic seizures, many scientists including Racine (1978) have turned their attention to the underlying mechanisms of kindling, in neurotransmitter systems and intracellular mechanisms, as well as genes.
Goddard’s experiments suggest that the processes underlying kindling and learning interconnect and possibly have similar underlying mechanisms. Kindling is of particular importance in disorders where recurrence is involved, in addictions (relapse) and mood disorders (recurrent episodes), but its underlying mechanisms are yet to be refined by empirical investigations.
Drug sensitization is a process frequently encountered in the literature of the field of addictions and pharmacology, and it is an essential process toward the understanding of drug action and use. Drug sensitization is a type of sensitization, and it refers to an increase in drug effect upon continual exposure to a drug in the organism, which was previously exposed to the drug. With repeated drug administration, gradual and incremental neuroadaptations are produced, which make animals hypersensitive to the specific drugs. Even though users or abusers will be keeping the same dosage levels, drug effects will be greater and greater; therefore they would become intoxicated even in small doses. Using repeatedly a drug but with some pauses in between causes greater sensitization compared to taking a single dosage or even taking repetitively the drug. Moreover, sensitization is promoted if periods of use are alternated with periods of abstinence. When a person who is sensitized let’s say to cocaine and abstains from use for some time, he/she is at risk of fatal overdosing at reuse (Steketee & Kalivas, 2011, Robinson & Berridge, 2008). Known addictive substances, where sensitization has been observed in, are cocaine, amphetamines, morphine, nicotine, and even alcohol; importantly not all drugs are subject to sensitization, mostly stimulants. In addition, the selected route of drug administration as sensitization is influenced by the speed or the time it takes for a drug to reach the brain. Sensitization in the case of drugs is long lasting with its effects on behavior and cognition lasting for years even with abstinence; however factors such as the time lapse between dosages, the choice of drug, the age and sex of the user, and genetics influence the strength of sensitization. Due to these factors, vulnerability to sensitization differs between individuals Steketee & Kalivas (2011). That provides an insight into the long-asked question of why some users become addicts while others do not get addicted. The sensitization of behavior and other psychological or psychomotor functions implies neural sensitization. Drugs seem to alter or reorganize neural systems and neurotransmitters, and even though causal relationships are yet to be established, neuroadaptations seem permanent. The permanency of changes in neurotransmitter circuits has crucial implications on the matter of cravings and relapse. Of special importance is the sensitization of the mesolimbic pathway of the mesotelencephalic dopamine system. Since dopamine is responsible for the motivation to go after pleasure and happiness and fulfill our “wants,” drugs come to jeopardize this process by making dopamine hyper-reactive, consequently increasing the prominence of drug cues, hence the intense cravings Robinson & Berridge (2008). In the matter of cravings and relapse, kindling is thought to be implicated. The aforementioned comprise the “incentive sensitization” theory of addiction developed by Berridge and Robinson (1998) and is noteworthy of further reading.
Drug sensitization is a complex process influencing drug users in a cellular level and in consequence in a behavioral level.
Sensitization is one of the simplest forms of non-associative learning, and it is of significant value as it has helped organisms to adapt in potentially dangerous situations and evolve. While sensitization’s underlying mechanisms are still under investigation, research thus far has been able to provide data for the better understanding of learning phenomena and the appearance and treatment of pathologies.
- Morris, R., Anderson, E., Lynch, G., & Baudry, M. (1986). Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate receptor antagonist, AP5. Nature, 319, 774–776. https://doi.org/10.1038/319774a0.