Drug addiction has been proposed as a form of Hebbi‑ an learning, as it creates changes in neural networks by strengthening or weakening some synapses. Similar chang‑ es occur during natural reward learning and it is believed that they are stored as encoded information-engrams. It has been suggested that drugs of abuse hijack these en‑ grams to create extremely durable forms of memories. Therefore, in this study, we aimed to test for similarities between initial exposure to an addictive substance and a natural form of learning. As a model of “addictive” learn‑ ing we chose intraperitoneal (IP) cocaine injections, while sucrose self-administration served to represent a natural form of learning. To distinguish different neuronal popu‑ lations, transgenic mice with labeled GABAergic neurons were used. All experiments were performed with contra‑ distinction between inhibitory and excitatory neurons. A series of electrophysiology experiments were performed on a specific brain pathway: the connection between pos‑ terior basolateral amygdala (pBLA) and the central medi‑ al amygdala (CeM). This pathway was recently shown to process positive memories. To ensure pathway specificity, viruses were injected into pBLA allowing for channeloro‑ dopsin2 expression in neurons. Synaptic changes were tested by whole-cell patch clamp electrophysiological re‑ cordings with the use of optogenetic stimulation. Results from electrophysiological recordings were confirmed by confocal microscopy. For this purpose brain slices were im‑ munolabeled with an antibody against c-Fos protein, which is a marker of neural plasticity. Our results indicated that indeed both cocaine IP injection and sugar administration changed the pBLA-to-CeM pathway in the same manner. In these structures we observed generation of silent synaps‑ es—immature synaptic contacts. Silent synapses contain mostly NMDA receptors(and not AMPA receptors) and may function as substrates for increased learning. Expression of c Fos protein also indicated that both sugar and cocaine contributed to structural changes in neurons in CeM. Addi‑ tionally, these changes were independent of cell-type (in‑ hibitory or excitatory). Thus, drug exposure affects a path‑ way that processes positive memories and engages similar neurons that natural learning does. Our results shed light on the debate surrounding of addiction as a form of simple, appetitive learning.
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