Istituto Di Neuroscienze - CNR

 

Neural mechanisms underlying neuropsychiatric disorders: focus on addiction

Research summary

The research in our laboratory is primarily focused upon understanding neural substrates that underlie reward, drug abuse and dependence.

Beside studying the acute mechanisms through which drugs of abuse affect neuronal activity, we are particularly intrigued by the long lasting functional remodeling that occur within specific brain circuits following prolonged exposure to abused drugs.

We are also interested in investigating the bidirectional relationship between drug use disorders, environmental and genetic factors, and mental illnesses (such as schizophrenia).

 

The main experimental approach used in the laboratory is electrophysiology (single unit, whole cell patch clamp, and EEG recordings) in combination with pharmacological, behavioural, and genetic tools.
Most recently we have expanded our list of topics and techniques to explore an innovative therapeutic strategy in epilepsy which relies on the interaction between PPAR-alpha and nicotinic acetylcholine receptors.

   

 

Research’s Topics

Characterization of the reward-aversion circuitry
Short and long term consequences of cannabinoid exposure during adolescence and adulthood
Cellular and neuronal underpinnings of increased vulnerability to addiction
Novel therapeutic strategies for addiction and epilepsy
Risk factors for neuropsychiatric disorders

Representative publications

Justinova Z, Mascia P, Wu HQ, Secci ME, Redhi GH, Panlilio LV, Scherma M, Barnes C, Parashos A, Zara T, Fratta W, Solinas M, Pistis M, Bergman J, Kangas BD, Ferré S, Tanda G, Schwarcz R, Goldberg SR (2013)
Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid. Nat Neurosci. 16(11):1652-61.

Puligheddu M, Pillolla G, Melis M, Lecca S, Marrosu F, De Montis MG, Scheggi S, Carta G, Murru E, Aroni S, Muntoni AL, Pistis M (2013).
PPAR-alpha agonists as novel antiepileptic drugs: preclinical findings. PLoS One. 8(5):e64541.

Lecca S, Melis M, Luchicchi A, Muntoni AL, Pistis M (2012).
Inhibitory inputs from rostromedial tegmental neurons regulate spontaneous activity of midbrain dopamine cells and their responses to drugs of abuse. Neuropsychopharmacology 37(5):1164-76.

Lecca S, Melis M, Luchicchi A, Ennas MG, Castelli MP, Muntoni AL, Pistis M (2011).
Effects of drugs of abuse on putative rostromedial tegmental neurons, inhibitory afferents to midbrain dopamine cells. Neuropsychopharmacology 36(3):589-602.

Melis M, Pillolla G, Luchicchi A, Muntoni AL, Yasar S, Goldberg SR, Pistis M (2008)
Endogenous fatty acid ethanolamides suppress nicotine-induced activation of mesolimbic dopamine neurons through nuclear receptors. J Neurosci. 28(51):13985-94.

Muntoni AL, Pillolla G, Melis M, Perra S, Gessa GL, Pistis M (2006).
Cannabinoids modulate spontaneous neuronal activity and evoked inhibition of locus coeruleus noradrenergic neurons. Eur J Neurosci. 23(9):2385-94.

Pistis M, Perra S, Pillolla G, Melis M, Muntoni AL, Gessa GL (2004).
Adolescent exposure to cannabinoids induces long-lasting changes in the response to drugs of abuse of rat midbrain dopamine neurons. Biol Psychiatry. 2004 Jul 15;56(2):86-94.

 

Lab team

Miriam Melis
Claudia Sagheddu
Sonia Aroni
Marta De Felice