TY - JOUR
T1 - Δ9-Tetrahydrocannabinol During Adolescence Attenuates Disruption of Dopamine Function Induced in Rats by Maternal Immune Activation
AU - Lecca, Salvatore
AU - Luchicchi, Antonio
AU - Scherma, Maria
AU - Fadda, Paola
AU - Muntoni, Anna Lisa
AU - Pistis, Marco
PY - 2019/9/6
Y1 - 2019/9/6
N2 - The combination of prenatal, such as maternal infections, and postnatal environmental insults (e.g., adolescent drug abuse) increases risks for psychosis, as predicted by the two-hit hypothesis of schizophrenia. Cannabis abuse during adolescence is widespread and is associated with increased risk of psychoses later in life. Here, we hypothesized that adolescent Δ9-tetrahydrocannabinol (THC) worsens the impact of prenatal maternal immune activation (MIA) on ventral tegmental area (VTA) dopamine cells in rat offspring. Additionally, since substance abuse disorder is particularly prevalent among schizophrenia patients, we also tested how VTA dopamine neurons in MIA offspring respond to acute nicotine and cocaine administration. We used a model of neurodevelopmental disruption based on prenatal administration of the polyriboinosinic-polyribocytidilic acid [poly (I:C)] in rats, which activates the maternal immune system by mimicking a viral infection and induces behavioral abnormalities and disruption of dopamine transmission relevant to psychiatric disorders in the offspring. Male offspring were administered THC (or vehicle) during adolescence (PND 45–55). Once adult (PND 70–90), we recorded the spontaneous activity of dopamine neurons in the VTA and their responses to nicotine and cocaine. MIA male offspring displayed reduced number, firing rate and altered activity pattern of VTA dopamine cells. Adolescent THC attenuated several MIA-induced effects. Both prenatal [poly (I:C)] and postnatal (THC) treatments affected the response to nicotine but not to cocaine. Contrary to our expectations, adolescent THC did not worsen MIA-induced deficits. Results indicate that the impact of cannabinoids in psychosis models is complex.
AB - The combination of prenatal, such as maternal infections, and postnatal environmental insults (e.g., adolescent drug abuse) increases risks for psychosis, as predicted by the two-hit hypothesis of schizophrenia. Cannabis abuse during adolescence is widespread and is associated with increased risk of psychoses later in life. Here, we hypothesized that adolescent Δ9-tetrahydrocannabinol (THC) worsens the impact of prenatal maternal immune activation (MIA) on ventral tegmental area (VTA) dopamine cells in rat offspring. Additionally, since substance abuse disorder is particularly prevalent among schizophrenia patients, we also tested how VTA dopamine neurons in MIA offspring respond to acute nicotine and cocaine administration. We used a model of neurodevelopmental disruption based on prenatal administration of the polyriboinosinic-polyribocytidilic acid [poly (I:C)] in rats, which activates the maternal immune system by mimicking a viral infection and induces behavioral abnormalities and disruption of dopamine transmission relevant to psychiatric disorders in the offspring. Male offspring were administered THC (or vehicle) during adolescence (PND 45–55). Once adult (PND 70–90), we recorded the spontaneous activity of dopamine neurons in the VTA and their responses to nicotine and cocaine. MIA male offspring displayed reduced number, firing rate and altered activity pattern of VTA dopamine cells. Adolescent THC attenuated several MIA-induced effects. Both prenatal [poly (I:C)] and postnatal (THC) treatments affected the response to nicotine but not to cocaine. Contrary to our expectations, adolescent THC did not worsen MIA-induced deficits. Results indicate that the impact of cannabinoids in psychosis models is complex.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85073057020&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31551729
U2 - https://doi.org/10.3389/fnbeh.2019.00202
DO - https://doi.org/10.3389/fnbeh.2019.00202
M3 - Article
C2 - 31551729
SN - 1662-5153
VL - 13
JO - Frontiers in behavioral neuroscience
JF - Frontiers in behavioral neuroscience
M1 - 202
ER -