Drug Reinforcement in a Rat Model of Attention Deficit/Hyperactivity Disorder – The Spontaneously Hypertensive Rat (SHR)

Abstract

The co-occurrence of drug addiction in adults with attention deficit hyperactivity disorder (ADHD) is very common, but its etiology remains largely unknown. Therefore, animal models to study this kind of psychiatric comorbidity are needed. The Spontaneously Hypertensive Rat (SHR) strain shows neurochemical and behavioral characteristics which make it a suitable model of ADHD. Compared with their normotensive controls (Wistar-Kyoto) and with some other rat strains, SHR rats drink more ethanol and are more sensitive to its anxiolytic/stimulant effects. They also show increased sensitivity to psychostimulants, opioids and cannabinoids. Furthermore, chronic treatment with methylphenidate, the first-choice drug to treat ADHD, during adolescence, changes the ethanol intake and the behavioral effects of cocaine in adult SHR rats. Regarding sex differences, females are more sensitive to psychostimulants and drink more ethanol than males, an important condition because in adulthood, more females suffer from ADHD than males. Taken together, the reviewed findings indicate that the SHR strain is a promising tool for studies on drug addiction and, possibly, its relationship with ADHD.

Methylphenidate treatment in the spontaneously hypertensive rat: influence on methylphenidate self-administration and reinstatement in comparison with Wistar rats

“…Of course, there are other variables that need to be addressed in relation to interpreting the potential clinical significance of the present results (for review, see Volkow and Insel 2003). Furthermore, some authors question the validity of the SHR to model ADHD (for review, see Van der Kooij and Glennon 2007) and the use of SHR to demonstrate ADHD, and ADHD and vulnerability to substances of abuse is not yet an established technique (Vendruscolo et al 2009;dela Peña et al 2010). Therefore, caution should be exercised when interpreting the present findings.…”

“…Accordingly, the SHR differs from its normotensive control strains (Wistar Kyoto and Sprague-Dawley rats) in response to the locomotorstimulating effects of methylphenidate (Yang et al 2003). The SHR appears to exhibit a hypofunctional mesolimbic dopamine (DA) system (Russell et al 1995), and this feature (which also produces the ADHD-like symptoms in this rat strain) ) may alter its response to certain substances (for review, see Vendruscolo et al 2009). Dysfunction in the DAergic system is implicated in the development of drug addiction behaviors (Feltenstein and See 2008).…”

Neuroadaptations Involved in Long-Term Exposure to ADHD Pharmacotherapies: Alterations That Support Dependence Liability of These Medications

“…In fact, it has been reported in the past that humans display interindividuality in behavioral responses to psychostimulants (Segal and Kuczenski, 1987;Piazza et al, 1989;Hooks et al, 1991). Thus, although still in its infancy, some investigations have been started considering differential response between rat strains representing the normal population (Wistar rats, Sprague-Dawley rats), from those which mimic the behavioral aberrations seen in ADHD, the SHR (for reviews see Askenasy et al, 2007;Vendruscolo et al, 2009). The advantage of doing experiments in animal models is that we deal with a simpler system and data obtained from these experiments may be easier to interpret to that of the clinical case (Sagvolden and Sergeant, 1998).…”

Comorbidade entre o transtorno de déficit de atenção/hiperatividade e o abuso e dependência de álcool e outras drogas: evidências por meio de modelos animais

“…nih.gov/pubmed/). Embora a pesquisa nesta área esteja em estágio bem inicial, os resultados abordados a seguir foram resumidos em nossa recente revisão 4 e sugerem que os ratos SHR sejam mais sensíveis aos efeitos comportamentais de psicoestimulantes (conforme citado anteriormente, substâncias desta classe constituem farmacoterapia de primeira escolha no tratamento do TDAH), canabinoides e opioides, do que outras linhagens de ratos (Tabela 1). Diferentes linhagens ("raças") de ratos podem apresentar diferentes níveis de sensibilidade e consumo de drogas, refletindo, possivelmente, diferenças neurobiológicas entre os indivíduos.…”

“…As implicações deste padrão comum nas alterações neurofisiológicas e no controle da inibição de respostas comportamentais em ambos os transtornos constituem foco de vários estudos e suas possíveis relações podem ser observadas na hipótese apresentada em recente publicação 2 Apesar do reconhecimento da expressiva relação entre TDAH e ADAD por parte da comunidade médica e científica, as pesquisas e a etiologia desta comorbidade psiquiátrica permanecem inconclusivas, em grande parte devido à escassez de modelos animais. Em recente revisão de nosso grupo sobre este tópico 4 , foi destacado que vários modelos animais de TDAH tem sido propostos e, embora criticados, estes modelos têm propiciado avanços importantes para o conhecimento na área. Dentre estes, o modelo animal de TDAH mais validado e utilizado é constituído pelos ratos espontaneamente hipertensos (SHR).…”