Indiana University-Purdue University Indianapolis (IUPUI) / Alcohol-paired cues invigorate alcohol-seeking and drinking behaviors in both rodents and individuals with alcohol use disorder (AUD). Additionally, genetic susceptibility plays a key role in alcohol addiction behaviors. Alcohol preferring (P) rats model both genetic vulnerability and symptoms of AUD. The basolateral amygdala (BLA), prefrontal cortex (PFC), hippocampus (HC) and nucleus accumbens (NA) are important brain regions involved in cued alcohol seeking. These regions are interconnected and their functional connections are hypothesized to be critical in the expression of motivated behaviors. Electrophysiological recordings in these four regions were collected in P rats engaged in a cued alcohol task. Data were filtered in the theta band (5-11 Hz) and segregated by behavioral epoch. The phase locking index γ was computed and used to measure strength of phase locking between signals from any two brain regions. The cross correlation between the amplitude of two signals was used to determine directionality. PFC-NA synchrony increased after stimuli presentation and remained elevated, relative to baseline synchrony. PFC-NA synchrony was also stronger for trials in which the animal made three or more lever presses (rewarded; R), compared to trials in which the animal responded fewer than three times (not-rewarded; NR). During lever pressing, PFC-BLA, NA-HC and PFC-HC synchrony was stronger after presentation of the DS+, in R compared to NR trials. NA-HC and PFC-BLA synchrony was stronger when responses were withheld in extinction, relative to conditioning. These data inform our knowledge of how corticolimbic connections are involved in cued ethanol seeking behaviors.

Implications for the endocannabinoid system in global cerebral ischemia has not been clearly defined. Ischemia produces an excitotoxic environment that is severely damaging to neurons, causing degradation of cell membrane and ultimately cell death. Contradicting research suggests both the benefits and adverse effects of endocannabinoids on neurological injury. Due to the excitotoxic nature of ischemic injury, and the mechanisms at play with endocannabinoid agonists, such as increased transmission of dopamine and glutamate, it is suspected that endocannabinoid antagonists, such as AM251, may a provide cell protection.40 male Wistar rats were separated into 4 groups (n=10/group). The first group of rats were administered AM251 (2 mg/kg, i.p) 30 minutes prior to global cerebral ischemia (four vessel occlusion), while the second group were given AM251, 30 minutes prior to sham surgery. Finally the last two groups were given a vehicle control instead of AM251 and given either ischemia or the sham surgery. Behavioural testing, open field test and elevated plus maze, took place after a five day recovery period following ischemia. Immunohistochemical analyses were performed using to mark tyrosine hydroxylase (TH) and dopamine receptor 1(DRD1) to compare dopamine function amongst groups. Cell survival was also evaluated using thionin staining. Ischemia induced significant reduction in dopamine within the mesolimbic circuit, including: ventral tegmental area, nucleus accumbens, CA3 & CA1 of the hippocampus, and basolateral amygdala. These reductions in dopamine transmission by global ischemia were partially or fully reversed when AM251 was given beforehand. Furthermore, cell survival was increased in the CA1 from treatment of AM251. Behavioural results show similar results that AM251 reversed emotional irregularities associated with ischemia insult. The endocannabinoid antagonist AM251 improves deficits in dopamine function, prevents cell death and regulates emotionality when given prior global cerebral ischemia.

Implications for the endocannabinoid system in global cerebral ischemia has not been clearly defined. Ischemia produces an excitotoxic environment that is severely damaging to neurons, causing degradation of cell membrane and ultimately cell death. Contradicting research suggests both the benefits and adverse effects of endocannabinoids on neurological injury. Due to the excitotoxic nature of ischemic injury, and the mechanisms at play with endocannabinoid agonists, such as increased transmission of dopamine and glutamate, it is suspected that endocannabinoid antagonists, such as AM251, may a provide cell protection.40 male Wistar rats were separated into 4 groups (n=10/group). The first group of rats were administered AM251 (2 mg/kg, i.p) 30 minutes prior to global cerebral ischemia (four vessel occlusion), while the second group were given AM251, 30 minutes prior to sham surgery. Finally the last two groups were given a vehicle control instead of AM251 and given either ischemia or the sham surgery. Behavioural testing, open field test and elevated plus maze, took place after a five day recovery period following ischemia. Immunohistochemical analyses were performed using to mark tyrosine hydroxylase (TH) and dopamine receptor 1(DRD1) to compare dopamine function amongst groups. Cell survival was also evaluated using thionin staining. Ischemia induced significant reduction in dopamine within the mesolimbic circuit, including: ventral tegmental area, nucleus accumbens, CA3 & CA1 of the hippocampus, and basolateral amygdala. These reductions in dopamine transmission by global ischemia were partially or fully reversed when AM251 was given beforehand. Furthermore, cell survival was increased in the CA1 from treatment of AM251. Behavioural results show similar results that AM251 reversed emotional irregularities associated with ischemia insult. The endocannabinoid antagonist AM251 improves deficits in dopamine function, prevents cell death and regulates emotionality when given prior global cerebral ischemia.