Sex differences in locomotor response associated with amphetamine administration

BENEDETTO, MM; BASMADJIAN OM; CETTRA-ZÁRATE, JA; RODRÍGUEZ, A; CAMBIASSO, MJ; PAGLINI, MG

Ciudad Autónoma de Buenos Aires, Buenos Aires

Congreso; SAN 2022 - SOCIEDAD ARGENTINA DE NEUROCIENCIA; 2022

SOCIEDAD ARGENTINA DE NEUROCIENCIA

Drug addiction is known as a chronic relapsing disease that affects both women and men. There are evidence that indicate the existence of sex-dependent differences in its etiology,epidemiology, and progression. Moreover, the neuroadaptive responses that underlie drug abuse and addiction may involve structural and functional synaptic plasticity processes.We aimed to evaluate whether there are sex dependent differences in the behavioral response and neuronal plasticity associated with amphetamine (Amph) exposure.For this, male and female thy-1 eGFP transgenic mice of 21 and 35 days (PN) were injected with Amph (4mg/kg) or vehicle and their locomotor activity was quantified; after 1 day withdrawal, the animals were challenged with the same administration protocol to evaluate sensitization. Four hours after the last Amph exposure, brain samples were obtained to analyze the density and type of dendritic spines of the pyramidal neurons of the CA1 hippocampal area.The results showed that acute Amph exposure induced hyperlocomotion in males at both PN 21 and 35, but not in females. Furthermore, re-exposure to the drug induced a greater locomotor response only in males, indicating sex differences in sensitization to Amph. Finally, preliminary results reveal that Amph induced an increase of stubby and mushroom spines in females at PN 21. These results show evidence of a sex dimorphic effect of Amph at behavioral level. Moreover, Amph induce hippocampal synaptic plasticity in females.