Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

Abstract

It has long been hypothesized that conditioning mechanisms play major roles in addiction. Specifically, the associations between rewarding properties of drugs of abuse and the drug context can contribute to future use and facilitate the transition from initial drug use into drug dependency. On the other hand, the self-medication hypothesis of drug abuse suggests that negative consequences of drug withdrawal result in relapse to drug use as an attempt to alleviate the negative symptoms. In this review, we explored these hypotheses and the involvement of the hippocampus in the development and maintenance of addiction to widely abused drugs such as cocaine, amphetamine, nicotine, alcohol, opiates, and cannabis. Studies suggest that initial exposure to stimulants (i.e., cocaine, nicotine, and amphetamine) and alcohol may enhance hippocampal function and, therefore, the formation of augmented drug-context associations that contribute to the development of addiction. In line with the self-medication hypothesis, withdrawal from stimulants, ethanol, and cannabis results in hippocampus-dependent learning and memory deficits, which suggest that an attempt to alleviate these deficits may contribute to relapse to drug use and maintenance of addiction. Interestingly, opiate withdrawal leads to enhancement of hippocampus-dependent learning and memory. Given that a conditioned aversion to drug context develops during opiate withdrawal, the cognitive enhancement in this case may result in the formation of an augmented association between withdrawalinduced aversion and withdrawal context. Therefore, individuals with opiate addiction may return to opiate use to avoid aversive symptoms triggered by the withdrawal context. Overall, the systematic examination of the role of the hippocampus in drug addiction may help to formulate a better understanding of addiction and underlying neural substrates.Addiction is a major worldwide health problem that results in maladaptive behavioral changes, some that can last a lifetime. This behavioral plasticity, often times maladaptive, must be associated changes in neural plasticity. In fact, it has been noted multiple times that there is a high degree of overlap between the neurobiology of learning and memory and the neurobiology of addiction

Aberrant structural–functional coupling in adult cannabis users

“…Interestingly, abnormal RC connectivity was found in the hippocampus, caudate, and pallidum (Figure 3D), regions of dense distribution of CB1 receptors in the brain (Svizenska, et al, 2008). In addition, the hippocampus and dorsal striatum play important roles in contextual learning and habit formation that maintain addictive behaviors (Koob and Volkow, 2016; Kutlu and Gould, 2016). In the present data, the hippocampus of CB users showed higher regional SC-FC coupling, while the caudate of users had a reduced coupling level (Figure 3E).…”

3d Synaptic Organization of the Rat Ca1 and Alterations Induced by Cocaine Self-Administration

“…The mechanisms underlying the causes of drug addiction are not entirely known, but it is thought that the processes of learning and memory are essential and that the hippocampus plays a key role in contextual conditioning and cocaine addiction 1,2 . In fact, addiction has been considered as a type of nonadaptive learning 3 .…”

Methamphetamine learning induces persistent nonmuscle myosin II-dependent spine motility in the basolateral amygdala

“…We also assessed CA1 spine motility for comparison. Like the BLA, the dorsal HPC is a critical component of the neural circuit supporting drug-associated memories and we have reported spine density increases in CA1 with METH learning, as in the BLA (31,43). However, METH memories do not bear the same vulnerability to disruption when NMII is specifically inhibited in CA1 and, unlike BLA spines, METH-induced CA1 spine density increases remain intact after systemic Blebb treatment (31).…”