Psychiatric Disorders as Vulnerability Factors for Nicotine Addiction: What Have We Learned from Animal Models?

Abstract

Epidemiological studies indicate a high prevalence of tobacco smoking in subjects with psychiatric disorders. Notably, there is a high prevalence of smoking among those with dependence to other substances, schizophrenia, mood, or anxiety disorders. It has been difficult to understand how these phenomena interact with clinical populations as it is unclear what preceded what in most of the studies. These comorbidities may be best understood by using experimental approaches in well-controlled conditions. Notably, animal models represent advantageous approaches as the parameters under study can be controlled perfectly. This review will focus on evidence collected so far exploring how behavioral effects of nicotine are modified in animal models of psychiatric conditions. Notably, we will focus on behavioral responses induced by nicotine that are relevant for its addictive potential. Despite the clinical relevance and frequency of the comorbidity between psychiatric issues and tobacco smoking, very few studies have been done to explore this issue in animals. The available data suggest that the behavioral and reinforcing effects of nicotine are enhanced in animal models of these comorbidities, although much more experimental work would be required to provide certainty in this domain.

Cognitive Dysfunction, Affective States, and Vulnerability to Nicotine Addiction: A Multifactorial Perspective

“…The effects of acute nicotine exposure on anxiety-like behavior is highly dependent on the task, dose, timing of testing, sex, strain, age, and basal anxiety levels of the animals ( 353 , 354 ). In the EPM, acute or subchronic systemic nicotine was found anxiolytic in some studies ( 280 , 285 , 293 ), anxiogenic at both low and high doses in others ( 288 , 289 , 292 , 294 ), or to have no effects ( 288 ), in rats.…”

An analysis of the rewarding and aversive associative properties of nicotine in the neonatal quinpirole model: Effects on glial cell line-derived neurotrophic factor (GDNF)

“…Tobacco dependence in individuals diagnosed with schizophrenia is 3–4 times higher than that of the general population (Le Foll et al, 2015). Our laboratory and collaborators have published a series of studies over the past 25 years that have demonstrated that rats neonatally treated with quinpirole (NQ), a dopamine D 2 /D 3 agonist during postnatal days (P) 1–11, 1–21, or 11–21, display an increase in sensitivity of the dopamine D 2 receptor throughout the animal’s lifetime without an increase in receptor number (Kostrzewa, 1995).…”

Chronic nicotine exposure attenuates the effects of Δ9‐tetrahydrocannabinol on anxiety‐related behavior and social interaction in adult male and female rats

“…Animal models are advantageous in studying the role of nicotine and other drugs in the development of anxiety‐related disorders and impaired social behaviors, although more research is necessary to demonstrate the mechanisms involved (Le Foll, Ng, Di Ciano, & Trigo, ). Behavioral measures established to model unconditioned anxiety include the light–dark emergence test (EM), the elevated plus‐maze (EPM) test, and the social interaction (SI) test (Arrant, Schramm‐Sapyta, & Kuhn, ; Crawley, ; File, Cheeta, & Kenny, ; Le Foll et al, ; Pellow, Chopin, File, & Briley, ).…”

“…Animal models are advantageous in studying the role of nicotine and other drugs in the development of anxiety‐related disorders and impaired social behaviors, although more research is necessary to demonstrate the mechanisms involved (Le Foll, Ng, Di Ciano, & Trigo, ). Behavioral measures established to model unconditioned anxiety include the light–dark emergence test (EM), the elevated plus‐maze (EPM) test, and the social interaction (SI) test (Arrant, Schramm‐Sapyta, & Kuhn, ; Crawley, ; File, Cheeta, & Kenny, ; Le Foll et al, ; Pellow, Chopin, File, & Briley, ). The emergence test assesses competing approach‐avoidance motivations and clinically effective anxiolytics significantly increase exploration of the open‐lit compartment whereas anxiogenics reduce exploration (Arrant et al, ; Chauoloff, Durand, & Mormede, ; Crawley, ; Merlo Pich & Samanin, ).…”

“…In comparison with animals confined to the closed arm, animals confined to the open arms show markedly elevated plasma corticosterone levels and more anxiety‐like behaviors (i.e., increased immobility, freezing behavior, and defecation; Pellow et al, ). The SI test assesses generalized anxiety behaviors in a social context measured by behaviors toward a conspecific, such as sniffing, following, grooming, and aggression; anxiolytic effects are generally inferred from increased social interaction, particularly in the absence of changes in locomotor activity reflecting nonspecific effects of a drug (File et al, ; Le Foll et al, ).…”